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T Wendler

Publications and source records attributed to T Wendler.

At least 19 recordsLinked to original sources

Modified DALI LDL-apheresis using trisodium citrate anticoagulation plus bicarbonate or lactate-buffered hemofiltration substitution fluids as primers.

BACKGROUND: DALI (direct adsorption of lipids) is the first LDL-apheresis technique able to adsorb low-density lipoprotein (LDL) and lipoproteina) directly from whole blood. In the standard procedure, acid citrate dextrose (ACD-A) is used as anticoagulation and the adsorber is rinsed with a specially manufactured priming solution (PS). Using neutral trisodium citrate (TSC) instead of ACD-A might improve the acid-base homeostasis during DALI apheresis; moreover, applying wholesale hemofiltration solutions instead of the special PS might avoid the use of two separate solutions for both priming before and reinfusion after the treatment, thus simplifiying the procedure. AIM: The present study was performed to test the effect of neutral (TSC) anticoagulation and of two different commercially available hemofiltration (HF) priming solutions on the efficacy and biocompatibility of DALI apheresis. MATERIALS AND METHODS: Five hypercholesterolemic chronic DALI patients were treated prospectively, on a weekly or biweekly basis, 3 times each by standard DALI-apheresis (A). by DALI using 4% TSC and bicarbonate-buffered HF BIC35-210 priming (B). as well as by DALI using 4% TSC and lactate-buffered HF 23 priming (C). After the sessions, the extracorporeal circuit (ECC) was rinsed with saline in study arm A and with the corresponding HF solutions in study arms B and C, respectively. RESULTS: Acute LDL-cholesterol reductions in the study arms A/B/C averaged 64/64/63%, for Lp(a) 62/64/62%, respectively (n=15). Clinically, all sessions were essentially uneventful and no clots were observed in the ECC. No major differences were found between the 3 study arms with respect to biocompatibility (elastase, C3a, thrombin-antithrombin, beta-thromboglobulin, bradykinin). CONCLUSION: DALI apheresis using TSC anticoagulation and HF solutions for both priming and reinfusion proved to be as safe and effective as the standard DALI apheresis. These modifications, however, further simplify the procedure.

Adult↗

Ex vivo biocompatibility of a new beta2-microglobulin hemoperfusion polymer.

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.

Antithrombin III↗

Improvement of hemorheology by DALI apheresis: acute effects on plasma viscosity and erythrocyte aggregation in hypercholesterolemic patients.

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) (Lp[a]), 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.

Adsorption↗

Extracorporeal plasma treatment in primary and recurrent focal segmental glomerular sclerosis: a review.

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.

Adult↗

Extracorporeal plasma treatment in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: a review.

This review summarizes the state of the art of apheresis in hemolytic uremic syndrome (HUS) and in thrombotic thrombocytopenic purpura (TTP). Both entities are characterized by thrombotic microangiopathy, hemolytic anemia, and thrombocytopenia. While HUS often presents with renal insufficiency, cerebral involvement is more common in TTP. Recently, in TTP, a primary or secondary lack of activity of a von Willebrand factor (vWF) degrading enzyme was made responsible for the presence of unusually large vWF multimers causing platelet aggregation and thrombus formation in the microvasculature. In contrast, in familial HUS, a factor H deficiency with uninhibited complement activation seems to play a role. Therapeutic plasma exchange (TPE) using fresh frozen plasma or cryosupernatant as the substitution fluid is indicated in acute TTP and atypical HUS without antecedent diarrhea. As a rule, it will show good effectiveness, especially in the former entity. HUS in pregnancy should be treated by instant delivery whereas postpartum HUS may resolve using protracted courses of TPE. In contrast, in thrombotic microangiopathy after bone marrow transplantation as well as in HUS due to cancer, mitomycin C, or after renal transplantation, TPE is of questionable value and indicated only as a last resort treatment.

Extracorporeal Circulation↗

Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial.

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

Adsorption↗

Heparin-free DALI LDL-apheresis in hyperlipidemic patients: efficacy, safety and biocompatibility.

BACKGROUND AND AIM OF STUDY: In routine DALI apheresis--the first technique for direct adsorption of lipoproteins from whole blood--heparin plus citrate (ACD-A) is used as anticoagulation regimen. However, recently several publications have warned of heparin-induced thrombocytopenia as a rare but potentially life-threatening complication of heparin administration (HIT type 2). The aim of the present study was therefore to test the efficacy and biocompatibility of DALI using a heparin-free anticoagulation regimen consisting exclusively of citrate. METHODS: Four symptomatic hypercholesterolemic patients on regular DALI apheresis were switched to the heparin-free protocol for two sessions each. Two of the patients were on oral anticoagulation using phenprocoumon. In the weekly sessions, 1.3 patient blood volumes were processed at a blood flow rate of 60 ml/min using ACD-A at a ratio of 1:20 (v/v) during adsorber priming and the session. RESULTS: Clinically, all sessions were essentially uneventful. Uncorrected lipoprotein reductions amounted to 65% for LDL-C, 62% for Lp(a), 53% for VLDL-C, 24% for HDL-C, 17% for triglycerides and 19% for fibrinogen. Cell counts remained virtually constant. No signs of hemolysis or clotting could be detected. Thromboplastin time (Quick) was slightly prolonged and partial thromboplastin time (PTT) moderately elevated in all patients. In contrast, whole blood coagulation time acc. to Lee-White and activated clotting times were increased only in orally anticoagulated patients. Biocompatibility in terms of complement, leukocyte and thrombocyte activation was excellent. Bradykinin activation was moderate peaking at 3038 pg/ml in the efferent line. Systemic thrombin-antithrombin complex (TAT) reflected perfect anticoagulation in orally anticoagulated patients and adequate anticoagulation in the patients without phenprocoumon. CONCLUSION: In this pilot study, heparin-free DALI apheresis was safe and effective and may thus be performed in LDL-apheresis dependent patients who suffer from heparin intolerance.

Adsorption↗

Cooperative image workstation based on explicit models of diagnostic information requirements.

A medical image workstation designed to act as a cooperative dialogue partner in diagnostic radiology has been conceived, and a prototype has been made. The system can automatically select relevant information (eg, from current and previous examinations) and generate a meaningful and appropriate image arrangement on the display screen. For a number of routinely performed tasks in radiology, the users' interaction may be as simple as switching from one patient to the next. This is shown to considerably simplify and speed up radiological image access and presentation, saving the user time and effort. The cooperative system response is based on explicit (formalized and computer-accessible) models of diagnostic information requirements. These models are context dependent and take into account that diagnostic information needs vary with radiological work procedures, workstation users, and patient cases. Initial models have been acquired from expert radiologists in two European hospitals and were integrated in a cooperative workstation prototype. For the representation of models, rule-based and object-oriented techniques were applied. The rule base was designed with a distinct modular structure, separating between rule sets for general, task-dependent, and user-dependent information requirements. The installed rule-based mechanism also offers a solution for the automatic prefetching of images to avoid transmission delays in the course of diagnostic work sessions. The first part of the report reviews the objectives for the design of cooperative workstation user interfaces and explains the benefits from the users' point of view. In the second part, the acquisition, structuring, formalization, and representation of context-dependent information requirement models is described. The rule-based model is explained using examples. A layered workstation architecture consisting of model, object, and real-time layers is presented. Difficulties in the implementation of cooperative workstations are discussed that point to future research topics and standardization efforts.

Diagnostic Imaging↗