: Low‐density lipoprotein (LDL) apheresis is a last‐resort treatment for hypercholesterolemic patients resistant to conservative lipid‐lowering therapy. In the extracorporeal circuit, LDL, Lp(a) and ...coagulation factors are selectively eliminated, while the beneficial proteins like high‐density lipoprotein, albumin and immunoglobulins are returned to the patient. Clinical effects of LDL apheresis comprise improvement of symptoms like angina and exercise tolerance, reduction of clinical coronary events like unstable angina, need for angioplasty or bypass operation, myocardial infarction and ultimately coronary mortality. The reduction of atherogenic lipoproteins and of coagulation factors by LDL apheresis (LA) positively influences hemorheology, endothelial function and coronary reserve. In the controlled LAARS, LA significantly improved the electrocardiographic signs of myocardial ischemia in the treadmill test. In angiographically controlled trials such as LARS and L‐CAPS, a reduction of progression of coronary lesions was observed; in favorable cases, regression of the stenoses could be documented. In addition, in the LDL apheresis coronary morphology trial, LA decreased the coronary plaque area. The Hokuriku trial documented a 72% decrease of coronary events (MACE) in the LA group vs. controls treated only by statins. In longitudinal studies, the incidence of MACE after regular LA decreased compared with the preapheresis period in the same patients. Apart from coronary heart disease, recent studies indicate a positive effect of LA also on carotid artery stenoses and peripheral vascular disease. Prospective randomized studies showed the beneficial effects of cascade filtration on age‐related macular degeneration and of heparin‐induced LDL precipitation apheresis on acute inner ear deafness.
This review summarizes the state of the art of apheresis in focal segmental sclerosing glomerulonephritis (FSGS) based on the current literature. FSGS is a major cause of nephrotic syndrome and renal ...insufficiency and has a high tendency to recur after renal transplantation. In many instances, treatment with steroids and/or immunosuppressive agents is without effect. Therapeutic plasma exchange (as well as immunoadsorption in some instances) was performed in primary (pFSGS) and recurrent (rFSGS) FSGS. Proteinuria could be improved and renal function was stabilized in 58% of rFSGS adults, in 74% of rFSGS children, and in 44% of pFSGS in adults. Treatment was successful if implemented early, i.e., in the stage of minimal change glomerulopathy before significant sclerosis had developed. This approach will probably be realistic only in the regular follow-up after transplantation. Furthermore, some patients with full-blown pFSGS were treated successfully in a prophylactic indication immediately prior to transplantation which decreased the incidence of recurrence to 26% in treated patients versus 54% in controls. Due to the uncontrolled study design and small patient cohorts in most trials, the major disadvantage of the reports currently available on the use of apheresis in FSGS is their low level of evidence from which the previous conclusions had to be drawn. Large prospective, controlled and randomized clinical trials are urgently needed for recommendations based on high-level evidence.
: Direct adsorption of lipids (DALI) is the first low‐density lipoprotein (LDL)‐apheresis technique capable of adsorbing LDL and lipoprotein (a) directly from whole blood. The adsorber consists of ...negatively charged polyacrylate ligands linked to a Eupergit matrix. Negatively charged ligands give rise to activation of bradykinin, which is rapidly degraded by the angiotensin converting enzyme (ACE). Thus, angiotensin converting enzyme inhibitors are contraindicated in DALI‐LDL‐apheresis. This is the first paper to describe the efficacy and safety of DALI‐LDL‐apheresis in patients treated with 50 mg of the angiotensin II‐receptor 1 antagonist (ARA) losartan. Two hypercholesterolemic patients were treated for 79 patient months with weekly or biweekly DALI sessions (N = 221 sessions). Approximately 1.4 patient blood volumes were treated per session. Acute reductions of LDL‐cholesterol (63%) and lipoprotein (a) (62%) exceeded 60% and laboratory safety parameters remained in the apheresis typical range. Mean bradykinin plasma levels peaked in the efferent line post‐adsorber at 1000 mL of treated blood volume; 467 fmol/mL (N = 6 sessions) in the ARA‐treated patients and 671 fmol/mL (N = 9 sessions) in a control group of three DALI patients without ARA medication (P = 0.69, n.s.). Clinically, the DALI sessions for the ARA‐treated patients were completely uneventful and blood pressure was not significantly different in the two groups. In summary, according to this retrospective pilot study, DALI‐LDL‐apheresis was shown for the first time to be safe and effective in patients on ARA medication.
: Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct ...adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low‐density lipoprotein (LDL)‐cholesterol and lipoprotein (a) (Lpa), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 ± 0.04 to 1.06 ± 0.3 mPa (−10%) while EA improved from 22.8 ± 4.4 to 13.3 ± 4.5 (arbitrary units) (−42%). LDL‐cholesterol, Lp(a), and very‐low‐density lipoprotein (VLDL)‐cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.
The kinetic theory of gases developed by Boltzmann and his group was one of the most remarkable theoretical achievements at the end of the 19th century. It opened up a vast phenomenological field ...that includes the chaotic world of turbulence and the reign of viscous fluids. Nonetheless, it is often left aside from general physics courses and down-to-earth applications because it seems too complicated. In this paper, we present a phenomenological model for a gas caught inside a cylinder with a moving piston, such as those of conventional combustion engines, and thus show that after a few simplifications the kinetic theory is comprehensible and allows satisfactory simulations even in non-equilibrium regimes.
There is no agreement among investigators of abyssal benthic foraminifera on the sieve-size of samples best suited for distribution studies; 63, 125, and 250 µm + sizes are commonly used. A faunal ...analysis of these fractions in two sets of deep-sea samples, one from the Caribbean, the other from the equatorial North Atlantic, demonstrates that a significant amount of information, including that on species diversity and dominance, is lost when the coarser sieves are used. The reported abundances of species in known water-mass associations of benthic foraminifera are not independent of specimen size. In an Antarctic Bottom Water assemblage from the Equatorial North Atlantic, a 250 µm threshold size obliterates the dominance of Epistominella exigua and inflates the proportion of Cibicides wuellerstorfi. Eponides turgidus, another dominant member of this assemblage, is almost absent in both the 125 and 250 µm + fractions. The same is true for Nuttallides decorata, the dominant benthic foraminifer in the Caribbean Bottom Water in the southeastern Venezuela Basin. Eponides polius, common in the Venezuela Basin assemblage, is absent in the coarsest fraction. We suggest that researchers choosing to work with coarser sieves in the context of their particular problems indicate what the proportions of common species would be if the 63 µm sieve is used. This test could be made with just a few samples.
ß
2
-microglobulin (ß
2
-m) is an 11.8 kD protein that is excreted by the kidneys. In renal insufficiency, it accumulates in the body and can result in AB amyloidosis with bone and joint destruction.
...Four modifications of a new ß
2
-m adsorbent material were tested for biocompatibility with human whole blood. 500 ml of heparinized blood from healthy human donors was perfused ex vivo through minicolumns (adsorber beads: divinylbenzene with different biocompatible coatings) in the single-pass mode. Blood samples were taken from the antecubital vein before and at the column outlet during the 50 min test runs.
Red and white cell counts remained virtually constant. No signs of hemolysis could be detected. Thrombogenicity of the columns was low as shown by the insignificant platelet loss, only slight platelet activation and moderate thrombin-antithrombin formation. There was no activation of leukocytes nor monocytes. Complement and bradykinin activation was minimal. Electrolyte concentrations and pH remained essentially constant.
In conclusion, this new ß
2
-m adsorbent material exhibited favorable biocompatibility features in our ex vivo model and is thus a promising candidate for future clinical ß
2
-m hemoperfusion studies in patients.
Beta2-microglobulin (beta2-m) is an 11.8 kD protein that is excreted by the kidneys. In renal insufficiency, it accumulates in the body and can result in AB amyloidosis with bone and joint ...destruction. Four modifications of a new beta2-m adsorbent material were tested for biocompatibility with human whole blood. 500 ml of heparinized blood from healthy human donors was perfused ex vivo through minicolumns (adsorber beads: divinylbenzene with different biocompatible coatings) in the single-pass mode. Blood samples were taken from the antecubital vein before and at the column outlet during the 50 min test runs. Red and white cell counts remained virtually constant. No signs of hemolysis could be detected. Thrombogenicity of the columns was low as shown by the insignificant platelet loss, only slight platelet activation and moderate thrombin-antithrombin formation. There was no activation of leukocytes nor monocytes. Complement and bradykinin activation was minimal. Electrolyte concentrations and pH remained essentially constant. In conclusion, this new beta2-m adsorbent material exhibited favorable biocompatibility features in our ex vivo model and is thus a promising candidate for future clinical beta2-m hemoperfusion studies in patients.
