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Biomedical subjects

Peter Kuehnl

Publications and source records attributed to Peter Kuehnl.

4 recordsLinked to original sources

New trends in specific immunoadsorption.

Plasma exchange is widely accepted to remove pathogenic substances from patients' blood that cannot be eliminated otherwise like cholesterol in severe forms of familial hypercholesterolaemia or immunoglobulins and circulating immune complexes (CIC) in many autoimmune disorders. But dilution of other plasma proteins, as well as side effects and costs of substitution fluids, limit its efficiency. In immunoadsorption, the pathogen is bound specifically, generally no substitution fluids are needed and plasma can be conducted over the immunoadsorption columns as often as needed to achieve any reduction that one aims at, in some instances below the detection limit (e.g. HLA-antibodies in transplantations). The frequency of aphaereses is determined by the speed of the patients' improvement and the rebound of the eliminated substance, which can in some disorders be slowed down or stopped by concomitant immunosuppression. Generally, immunoadsorption is used in patients, where less expensive and demanding treatment options have failed, like severe hypercholesterolaemia, autoimmune disorders or hyperviscosity syndromes.

Autoantibodies↗

Binding of activated platelets to WBCs in vivo after transfusion.

BACKGROUND: During preparation and storage of apheresis concentrates, platelets are being activated. One of the alterations that occur during this process is an increased expression of P-selectin (CD62p) on the cytoplasmic surface of platelets. This neoepitope represents a ligand for the binding of platelets to WBCs. It has been suggested that the activation of platelets is associated with the sequestration of platelets after transfusion. In this in vivo study, the binding of platelets to WBCs was analyzed following transfusion of platelet concentrates (PCs). STUDY DESIGN AND METHODS: Double apheresis concentrates were prepared with two different cell separators. One of the split products was stored for 1 to 2 days and the other one for 3 to 5 days. Flow cytometry was applied to analyze the degree of platelet activation in vitro, and also to measure the extent of platelet binding to WBC subclasses in vivo after transfusion into patients. RESULTS: The results of this study show that platelet activation occurs during apheresis and storage of PCs. After transfusion of the PCs, no significant binding of platelets to T or B-cells could be detected. However, a significant binding of platelets to monocytes and neutrophil granulocytes occurs. While in Baxter PCs stored for 1-2 days the amount of platelet-leukocyte aggregates in vivo was higher compared to COBE PCs, no such difference could be detected anymore for the PCs stored for 3-5 days. CONCLUSION: This study demonstrates that binding of activated platelets occurs to monocytes and neutrophil granulocytes but not to T- and B-cells in the circulation after transfusion. In addition, the interaction of platelets and WBCs is dependent on the degree of P-selectin expression. Platelets showing a higher degree of activation adhere to WBCs to a higher degree than nonactivated platelets.

Adult↗

Influence of heparin coating of coronary stents and ex vivo efficacy of different doses of acetylsalicylic acid and ticlopidine in a pulsed floating model of recirculating human plasma.

Acute occlusion of stented coronary vessels still occurs in up to 3%. Activated platelets have been found to play a major role in the pathogenesis of these complications. We therefore analyzed the efficacy of a heparin coating of coronary stents and investigated the ex vivo efficacy of different antiplatelet drugs. Each of seven healthy volunteers was treated with each of the following medications for 7 days: ASA 100 mg/day, ASA 300 mg/day, ticlopidine 250 mg/day, and ticlopidine 500 mg/day. Three standardized in vitro silicon tubing models, one of them containing an uncoated stent, one a heparin-coated stent, and one without a stent (control) were filled with PRP and circulation was started. TOS in systems with heparin-coated stents was 2.4-times longer compared to systems with uncoated stents (P<0.001), and 1.5-times longer compared to the control (P<0.01). The increase of CD62p expression within the first 5 min was 2.5-times higher in systems with uncoated stents and 1.7-times higher in the control than in systems with heparin-coated stents (P<0.05). Aggregometry revealed significant medication- and dose-dependent inhibition of platelet aggregability for all medications. Heparin-coating of coronary stents reduces their thrombogenicity significantly. ASA and ticlopidine effectively reduce platelet activation ex vivo. The used in vitro system facilitates a reproducible method to estimate the thrombogenicity of coronary stents prior to in vivo trials.

Angioplasty, Balloon, Coronary↗

Th2 dominance of T helper cell response to preproinsulin in individuals with preclinical type 1 diabetes.

In human type 1 diabetes (T1D) autoantibodies to insulin precede clinical disease, while little is known about the contribution of insulin-specific T lymphocytes-in particular, T helper (Th) subsets. Here we have studied the in vivo primed cytokine response to preproinsulin in peripheral blood mononuclear cells (PBMCs) and two major Th cell subsets-CD45RO+ memory cells and CD45RA+ naive/resting cells-in 35 individuals with HLA-DRB1*04, DQB1*0302 diabetes risk marker: 12 patients with T1D, 12 autoantibody-positive (Ab+) individuals, and 11 healthy controls. Cytokine secretion (TNF-alpha, IFN-gamma, IL-2, IL-4, IL-5, and IL-10) was measured in the supernatants of the cultures stimulated with 21 overlapping preproinsulin peptides as well as proinsulin and insulin. In Ab+ individuals our results reveal higher IL-4 levels in CD45RO+ memory cells and higher IL-5 levels in CD45RA+ naive/resting cells, while higher IL-2 production was found in PBMCs. In contrast, in PBMCs of T1D patients higher IFN-gamma and IL-10 secretion was found. Our data delineate characteristic cytokine patterns in peripheral T lymphocytes from patients at different stages of the T1D development.

Adolescent↗