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Biomedical subjects

J Vermylen

Publications and source records attributed to J Vermylen.

At least 163 records · Page 9Linked to original sources
PubMed1990

R68070, a combined thromboxane/endoperoxide receptor antagonist and thromboxane synthase inhibitor, inhibits human platelet activation in vitro and in vivo: a comparison with aspirin.

We have investigated the effects of R68070 on platelet function in vitro and in vivo. The drug inhibits U46619-induced aggregation (IC50 = 1.2 x 10(-6) mol/L), blocks serum thromboxane formation (IC50 = 1 x 10(-7) mol/L), and increases serum prostaglandin (PG)E2 and 6-keto-PGF1 alpha levels, indicating that it combines thromboxane receptor blocking and thromboxane synthase inhibiting properties. The thromboxane-dependent aggregation of blood platelets is blocked by R68070, whereas no inhibition of thromboxane independent pathways occurs. A double-blind, randomized, cross-over study was performed on nine volunteers, comparing 400 mg placebo, 400 mg aspirin, and 400 mg R68070. Thromboxane-dependent aggregations were significantly inhibited by R68070 and by aspirin, the latter still having the most pronounced action. However, R68070 was clearly more powerful than aspirin (P less than .0005) in prolonging the bleeding time. Serum TxB2 formation was completely inhibited with both treatments, whereas serum 6-keto-PGF1 alpha and PGE2 and intralesional 6-keto-PGF1 alpha were inhibited after aspirin and stimulated after R68070. We conclude that R68070 inhibits platelet thromboxane synthase and its thromboxane receptor both in vitro and in vivo; local reorientation of cyclic endoperoxide metabolism toward prostacyclin induces a stronger inhibition of hemostasis than that produced by aspirin.

Aspirin↗
PubMed1990

Acquired protein C and S deficiency, inflammatory bowel disease and cerebral arterial thrombosis.

Thromboembolic complications may occur in inflammatory bowel disease. Recently, we had the opportunity to observe a case of a cerebral arterial thrombosis in a young patient with active ulcerative colitis. Investigation of blood coagulation revealed a temporary Protein C, Protein S and Factor II deficiency. To our knowledge, this is the first reported case of a temporary Protein C and S deficiency in a patient with thrombosis and inflammatory bowel disease.

Adult↗
PubMed1990

Autotransfusion during aorto-iliac surgery.

Red blood cell (RBC) quality and function during autotransfusion with the Solcotrans system were studied. Up to 64% (mean 999.5 +/- 310 ml) of the total volume of blood lost (mean 1895 +/- 707 ml) during operation in 10 patients undergoing elective abdominal aortic surgery was salvaged. No patient received homologous blood during surgery. Haemoglobin (Hb) and Haematocrit (PCV) values decreased but within acceptable limits. No evidence of DIC was found and renal function was unaffected. Mechanical and functional damage to the RBC was minimal and erythrocyte oxygen-carrying capacity was excellent. 2,3-DPGRBC concentration and RBC reduced glutathion were normal. The device was easy to handle and technical problems were not encountered. It was accurate in salvaging blood although the need for homologous blood was not entirely eliminated since four patients received homologous blood products in the postoperative period. No adverse clinical events occurred.

Aged↗
PubMed1990

Protein C deficiency associated with venous thromboembolism.

Protein C deficiency has been reported to be associated with a high risk for thromboembolism. We report three patients with protein C deficiency: one suffered from left renal vein thrombosis, another from recurrent venous thrombosis of the legs complicated by pulmonary embolism and the third from an extensive thrombosis of the splanchnic veins with partial Budd-Chiari syndrome. We discuss the unusual sites of venous thrombosis in protein C deficient patients, the factors which may act as thrombotic trigger and the strategy of long-term prevention.

Blood Protein Disorders↗
PubMed1990

Pharmacological manipulation of the thromboxane pathway in blood platelets.

Interference with blood platelet thromboxane A2 (TxA2)-formation using aspirin has proven to be clinically efficient in the prevention of arterial thrombosis. The protection, however, is far from absolute and during recent years we have witnessed the development of new classes of drugs with more specific impact on TxA2-dependent pathways of platelet activation. Thromboxane synthase inhibitors (TSI) act on the thromboxane synthase, thus preventing the formation of TxA2, and causing a shunting of the prostaglandin cyclic endoperoxide metabolism towards other prostanoids, such as the platelet inhibitory PGD2 and PGI2, the latter when endothelial cells are present that can 'steal' platelet derived cyclic endoperoxides. TSI, however, do not block the formation of the cyclic endoperoxides. Since those products themselves can also act on the TxA2-receptor, the net effect of a TSI will be the result of a complex balance of pro- and anti-aggregatory prostanoids. Known thromboxane receptor antagonists (TRA) inhibit the interaction of both TxA2 and the cyclic endoperoxides with the receptor in a competitive way, but do not change the relative levels of the different prostaglandins formed. The combination of the two actions leads to a stronger influence on in vivo, ex vivo and in vitro laboratory tests as can be seen when a TSI and TRA are used in combination, or when a drug is studied that has both characteristics. Additional data show that such a double-action drug is able to quickly reduce levels of beta-thromboglobulin, a marker for ongoing in vivo platelet activation, in patients with obstructive arterial disease.

Animals↗
PubMed1990

Non-receptor-mediated refractoriness in prostacyclin production by human endothelial cells in a continuous flow system is delayed by a low-molecular-weight plasma fraction devoid of reducing cofactors for peroxidase-catalysed reactions.

Using a microcarrier perfusion model, we have investigated the effects of a low-molecular-weight plasma fraction (mol. wt. less than 10,000) on the capacity of human umbilical vein endothelial cells (HUVECs) to synthesize and release prostacyclin (PGI2) during repeated stimulation with either calcium ionophore A23187 or arachidonic acid (AA). This plasma fraction (filtrate 10,000), which has recently been shown to contain most of the activity previously referred to as 'prostacyclin regulating plasma factor', delayed the exhaustion of the PGI2 generating capacity of the HUVECs during repeated stimulation with either inducer. No such effect was seen with whole plasma. The PGI2 regulatory activity of the filtrate was not significantly affected by removal of reducing cofactors for peroxidase-catalysed reduction of hydroperoxides, accumulation of which inhibits cyclooxygenase. In contrast, albumin added to the filtrate abolished its protective effect on endothelial PGI2 synthesis. We conclude that low-molecular-weight plasma constituents partially preserve the PGI2-generating capacity of human vascular endothelium during repeated stimulation. Under continuous flow conditions, as applied in our study, this effect appears not to be related to reducing cofactor activity for peroxidase-catalysed reactions. In whole plasma, this PGI2 regulatory activity may be partially masked by the presence of plasma proteins.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

[Angioplasty using a Nd:YAG laser with a sapphire probe].

Laser angioplasty with Sapphire Contact Probes coupled to a Nd:YAG laser followed by balloon angioplasty was performed in 30 patients with 26 femoropopliteal and 4 iliac artery occlusions. Mean length of the occlusions was 4.5 +/- 1.6 cm with a mean duration of occlusion of 7.06 +/- 6.18 months. Initial angiographic success was obtained in 25/30 (83%) procedures, including 3/4 successes in the iliac artery (75%) and 22/26 successes in the femoropopliteal artery (84%). Reason for failure was perforation in 2 patients, and subintimal passage of the probe in 2, and heavy calcification of the lesion in 1 patient. Early rethrombosis in 3 patients reduced the primary success rate to 73%. Peripheral emboli necessitating surgical intervention occurred in 2 patients. Of the 22 recanalized arteries 21 remained patent with a mean follow-up of 8.4 +/- 3.3 months. It remains to be determined whether the angiographic and clinical short and long term success rate of "laser assisted balloon angioplasty" will be greater than after thrombolysis or conventional balloon angioplasty.

Aged↗
PubMed1990

Urinary thromboxane B2 and 2,3-dinor-thromboxane B2 in the neonate born at full-term age.

We have developed a method for measurement of urinary 2,3-dinor-TXB2, which is a reflection of the actual rate of TXA2 synthesis by platelets in vivo. This determination was based on purification by high-pressure liquid chromatography and on measurement by RIA. After validation of the assay, we established the range of urinary Tx metabolites in healthy infants born at full-term during their first week of life. The 2,3-dinor-TXB2 levels were higher than in adults and declined gradually during the first seven days of life.

Chromatography, High Pressure Liquid↗
PubMed1990

Preliminary results of percutaneous transluminal atherectomy.

Percutaneous transluminal atherectomy with the Simpson atherectomy catheter was performed in 5 patients with severe atheromatous stenoses of the femoropopliteal arteries. In all patients plaque material was removed with successful restoration of vessel patency. Further clinical follow-up will have to determine whether recurrence rate of stenosis will be lower with this method than with conventional balloon angioplasty.

Arteriosclerosis↗
PubMed1990

Outpatient angiography.

Outpatient angiography of the abdominal aorta and the peripheral arteries of the under limbs was performed in 100 patients with complaints of peripheral vascular disease. In all patients small 5F catheters, a low-osmolar contrast medium and intraarterial digital subtraction angiography could reduce the local and general invasiveness of the angiographic procedure. Two complications occurred. In one patient thrombosis at the puncture site was noted. In another patient, an onset of angina pectoris was a minor and transitory complication. In 42 out of the 100 patients, treatment was conservative so that hospitalization could be avoided. With newer technical equipment angiography can be performed safely on an outpatient basis with important costsaving for the community. The late occurrence of some complications though, requires good information of the patient.

Adult↗
PubMed1989

Platelet aggregation in whole blood--studies with a platelet counting technique--methodological aspects and some applications.

We describe a method for measuring platelet aggregation in whole blood by single platelet counting. The importance of a low stirring speed (100 rpm) to obtain agonist-specific aggregation is stressed. Despite this low stirring speed, the sensitivity to agonists equals that of the turbidometric technique in platelet-rich plasma. The optimal concentration of formaldehyde for fixing the aggregates, the effects of storage times and anticoagulant are studied. Applicability to the study of platelet function inhibitors or of inherited platelet function disorders is illustrated. It is concluded that this technique, used under the appropriate conditions, combines the advantage of measuring platelet aggregation in a more physiologic environment with the advantages of the turbidometric technique such as high sensitivity.

Adenosine Diphosphate↗
PubMed1989

Characterization of N,N'-bis(3-picolyl)-4-methoxy-isophtalamide (picotamide) as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets.

Picotamide (G137 or N,N'-bis[3-picolyl]-4-methoxy-isophtalamide), a drug which has shown platelet inhibitory effects in vitro and ex vivo, was investigated for its mechanism of action on human platelets in vitro. This compound suppresses the aggregation of human platelets induced by arachidonic acid (IC50: 1.8 x 10(-5) M), low-dose collagen (IC50: 3.5 x 10(-4) M), U46619 (IC50: 1 1.4 x 10(-4) M) and by authentic TxA2 (IC50: 1 x 10(-4) M), without affecting the aggregation induced by A23187 or primary aggregation by ADP. Picotamide inhibits dose-dependently TxA2 synthesis by platelets (IC50: 1.5 x 10(-4) M) and enhances the formation of PGE2. Picotamide-treated platelets also favour the formation of PGI2 by aspirinated endothelial cells; in addition, the drug appears to exert a direct stimulatory effect on PGI2-synthesis, at least at high concentrations. Finally, in platelet-rich plasma stimulated with arachidonic acid, picotamide increases intraplatelet cAMP while no effects on cAMP are detected in unstimulated platelets. In conclusion, picotamide is a dual thromboxane-synthase inhibitor/thromboxane-receptor antagonist in human platelets and introduces a new class of agents potentially useful in antithrombotic therapy.

Arachidonic Acid↗
PubMed1989

Absence of potentiation with murine antiplatelet GPIIb/IIIa antibody of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in a canine venous thrombosis model.

F(ab')2 fragments of a murine monoclonal anti-platelet GPIIb/IIIa antibody (7E3) are a potent platelet aggregation inhibitor, which in a canine coronary artery thrombosis model accelerate lysis with recombinant tissue-type plasminogen activator (rt-PA) and prevent reocclusion (7). In the present study, we have investigated the potential value of platelet aggregation inhibition as adjunctive therapy to lysis of venous thrombi, by measuring the thrombolytic potency of 7E3-F(ab')2 and rt-PA used alone or in combination, in dogs with a 125I-fibrin labeled femoral vein thrombus. The dose-response of thrombolysis with rt-PA infused over 4 hours was linear: doses of 0.075 mg/kg, 0.15 mg/kg and 0.3 mg/kg produced 37 +/- 3, 57 +/- 11 and 83 +/- 4% lysis respectively, against a background value of 20 +/- 2%. With F(ab')2 fragments of 7E3 given as a bolus of 1.2 mg/kg, which saturated 70% of the platelet GPIIb/IIIa receptors and prolonged the bleeding to more than 30 min, lysis was not significantly increased over background. Combination of 0.3 or 0.6 mg/kg of 7E3-F(ab')2 with either 0.03 or 0.06 mg/kg of rt-PA did not produce more lysis than obtained with a comparable dose of rt-PA alone. No significant changes in plasma fibrinogen or alpha 2-antiplasmin were observed with either agent alone or with the combination. It is concluded that extensive inhibition of platelet aggregation does not potentiate the thrombolytic effect of rt-PA in this venous thrombosis model.

Animals↗
PubMed1989

Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients.

Recombinant human erythropoietin was administered for up to 40 weeks to nine patients on chronic haemodialysis. From the third week of administration onwards, not only haemoglobin and haematocrit but also the platelet count rose, the latter, however, transiently. Subnormal platelet aggregation before therapy also improved transiently and in parallel with the erythropoietin dosage. The bleeding time normalized in almost all patients. There were no major side-effects. We conclude that recombinant erythropoietin improves haemostasis in chronic haemodialysis patients by increasing the haematocrit and in addition transiently enhances platelet number and function.

Adult↗