bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUBSTITUTION THERAPY WITH ANTITHROMBIN III: CLINICAL EXPERIENCE WITH DECOMPENSATED LIVER CIRRHOSIS AND HEMORRHAGIC COMPLICATIONS
Authors: Lorenz R , Holweger M , Vogel GE , Classen M 
Published: August 2018

In patients with decompensated liver cirrhosis, the coagulation disorder requires therapy only when bleeding complications occur. As therapy involves the risk of triggering a consumption coagulopathy, the discussion here examines the beneficial effect of boosting the inhibitor Potential by supplementing the administration of fresh plasma with substitution of AT III concentrate. To investigate this question, we conducted a retrospective study on the clinical course in 19 patients with decompensated liver cirrhosis, hepatic encephalopathy and bleeding complications.The following treatment scheme was employed uniformly in all 19 cases: substitution of vitamin K 20 mg/d, heparin 100 - 300 U/h and fresh plaspna 2-4 bags/d. AT III concentrate (3 - 8 × 500 U/d Ky-bemin HS ) was administered additionally in group 1 (n=8), but was omitted in group 2 (n= 11). Both groups were statistically comparable with regard to initial laboratory findings (e.g. bilirubin, group 1: 11.7 ± 3.6 mg/dl; bilirubin, group 2: 10 ± 2.9 mg/dl) and encephalopathy Tcoma stages 1-2), with the exception of the two survivors in group - who had been in a precomatose stage (stages 0-1) and had bilirubin levels of 3 ± 1.5 mg/dl.A comparison oT both collectives shows a lethality of 62.5 % (n=5) for group 1, and of 81 % (n=9) for group 2. Clinically, the incidence of hemorrhagic complications in group 1 was 61 %, but 100 % in group 2, although laboratory analysis showed no differences in the parameters of systemic coagulation. As regards the other laboratory values, including the transaminases and blood count, there were only differences in the development of the bilirubin values which, in group 1, rose to -3 ± 4 mg/dl only during the terminal phase, but which, in group 2, began to rise continuously from the second day of treatment onwards 2nd reached values of 28 ± 8.6 mg/dl.It follows that, in patients with decompensated liver cirrhosis and bleeding complications, the administration of AT III concentrate (Ky-bernin HS ) as a supplement to conventional coagulation therapy, increases the survival rate and reduces the incidence of further bleeding. It is, however, not possible tc explain the cause of this effect from the analysis of the laboratory data for the systemic coagulation. Therefore, one may hypothesize that the effect is due to beneficial effect of AT III within microcirculation.
HAEMOSTASIS IN NATIVE WHOLE BLOOD: CLINICAL STUDIES WITH THE HAEMOSTATOMETER
Authors: Kovacs I B , Hutton R A , Kernoff P B A 
Published: August 2018

The haemostatometer is a new instrument which allows quantitative assessment of haemostasis by monitoring the pattern of haemostatic plug formation (HPF) which occurs in holes in polyethylene tubing through which unanticoagulated blood is flowing under standard conditions (1). The pattern and speed of blood coagulation, subsequent to HPF is also measured by the instrument. Eight healthy volunteers were tested before and 2hr, 5dy and 12dy after a single 600mg oral dose of aspirin. Maximum prolongation of HPF time occurred at 2hr (1.97 × baseline, p=<0.001) and the effect remained significant (p=<0.01) at 5dy. The pattern of the aspirin-induced effect on HPF was characteristic. The coagulation time was not affected by aspirin. In 4 patients with platelet release defects, the HPF time, but not the clotting time, was significantly prolonged (2.1 × controls, p= <0.01). In 4 patients with von Willebrand’s disease of different severities, platelet-collagen interaction was tested simultaneously with HPF by inserting a length of catgut into the tubing and measuring the time to cessation of blood flow (2).Both impaired HPF and ineffective formation of occlusive platelet thrombus on the catgut were observed. In haemophilia A patients, HPF time as well as clotting time was prolonged in some cases and in these, improvement of platelet function (shortened HPF time) occurred following factor VIII therapy. As diabetes mellitus may be associated with a prethrombotic state, 20 diabetics were tested and shown to have a shortened HPF time.(1) Gorog P, Kovacs I. Haemostasis, 16, 337-45, 1986. (2) Gorog P, Kakkar W. Amer J Clin Path, 86, 311-16, 1986.
PROTECTIVE ANTITHROMBOTIC ACTION OF THE PREPARATIONS FROM THE LEECHES HIRUDO MED ICINAL IS
Authors: Nikonov G , Baskova I 
Published: August 2018

Blood letting effect of the medicinal leeches is provided by antihaemostatic properties of the salivary gland secretion. We have demonstrated that the natural salivary gland secretion inhibits the vascular-platelets haemostasis and the contact stage of the intrinsic mechnism of blood coagulation but has no effect on the activation of extrinsic mechanism (Bui 1.Exp.Biol.Med.USSR 97, 6, 696; 8, 142, 1984). Leech prostaglandins (Dokl.Acad.Nauk USSR, 1987) and inhibitors of plasma kallikrein and Factor XI la are the main anti haemostatic agents of the leech saliva.The leech saliva does not change the main parameters of blood coagulation of the healthy animals, such as recalcification time, cephalin time, thrombin and prothrombin time 5, 15 and 25 min after intravenous injection. But the platelets aggregation stimulated by thrombin is diminished by 20% (n=30;p 0,02) Recalcification time, cephalin time and platelets aggregation reduced by intravenous injection of human serum is corrected by leech saliva.As the trigger mechanisms of haemostasis are very much alike the trigger mechanisms of thrombogenes?s, we investigated antithrombotic ability of the leech saliva, extracts of dried leeches and blood of intestinal gut. We used Wessler procedure of throm-bous formation in rats.The thrombous formation was diminished by 90% compared to control when 0.3 ml of the leech saliva (diluted with saline 1:4) was injected intravenously 2-4 hrs before injection of human serum. Thrombous formation was diminished by 40% when time interval was elongated to 24-28 hrs. Antithrombotic effect does not depend on the antithrombin activity of hirudin. It slightly decreased in case of oral administration and increased after the multiple intravenous injections or oral administration.Blood from the leech intestinal tract and other preparations from the leeches exhibit less distinct antithrombotic effect than the salivatory gland secretion.
DETERMINATION OF CHOLESTERYL HYDROXYOCTADBCADIENOATES IN VASCULAR TISSUE BY HPLC AND ITS RELEVANCE TO ATHEROSCLEROSIS
Authors: Heiremans J , Claeys M , Herman A G 
Published: August 2018

Accumulation of lipids in the intimal arterial layer, and of cholesterol esters in particular, has been recognised as an early and prominent phenomenon in atherogenesis. Several attempts have been made to link putative peroxidation of these lipids in vivo to causal or deteriorating etiological determinants of plaque formation. The occurrence in advanced human atheromata of oxidized derivatives of cholesteryl linoleate -a major polyunsaturated cholesterol ester species in plasma and vessel wall - has been described by Brooks et al. (Atherosclerosis, 1970,13,223) and a positive correlation between the amount of cholesteryl hydroxyoctadecadienoates (CHODES) and the stage of the lesion has also been reported. In addition Funk and Powell (J. Biol. Chem., 1985,260,7481) have found hydroxyoctadecadienoic acids in normal aorta of different species, wich were strikingly increased after alkaline hydrolysis of total lipids, and this in contrast with the arachidonic acid analogs. The aim of this study was to develop a sensitive and practical method for specific assay of CHODES, without resorting to laborious saponification and derivatisation procedures required for gas chromatographic analysis, which could moreover augment the risk for artefacts.Dog thoracal aorta was homogenised and lipids were extracted using the Folch method with CHCl3/CH30H;2/l containing 0.05mM butylated hydroxytoluene. Fractionation of CHODES from neutral lipids was carried out by thin-layer chromatography. For detection and quantification a high-performance liquid chromatography (HPI/2) assay method was developed, with UV monitoring at 232nm , a wavelength characteristic for conjugated dienes with vicinal hydroxyl function. Reference compounds and the internal standard for HPLC analysis were synthesized from linoleic acid and 10,13,16-docosatrienoic acid, respectively, by preparation of hydroxy fatty acids with soybean lipoxygenase and subsequent esterification to cholesterol esters with pancreas cholesterol esterase. Confirmation of the structural identity was obtained by mass spectrometry. Artefactual formation of CHODES ex vivo was investigated by subjecting radiolabeled cholesteryl linoleate through the analysis procedure. This method allows the specific detection of CHODES in non-atherosclerotic arteries which was hitherto only reported for human advanced atherosclerotic lesions and is proposed as a sensitive and specific probe for prospective survey of lipid peroxidation in atherosclerotic blood vessels.
AN IMPROVED METHOD FOR COVALENT IMMOBILISATION OF HEPARIN BY END POINT ATTACHMENT
Authors: Larm O , Adolfsson L , Gouda I , Malmberg A , Olsson P , Scholander E 
Published: August 2018

When creating a non-thrombogenic surface by immobilisation of heparin, most of the biological activity of heparin as it is expressed in blood should be retained after the coupling procedure. Consequently the chemical methods used in the immobilisation procedure shall be selected so that they do not, infavorably, affect the anti-thrombin (AT) binding site, the charge distribution and charge density of heparin.To ascertain that the AT-binding sequence is not involved in the coupling procedure, we have developed a method in which heparin is coupled by end point attachment (EPA). Heparin is partially degraded with nitrous acid and fragments with reactive aldehydo functions in the reducing terminal residues are formed. These are coupled to aminated surfaces by reductive amination. The primary amines have been introduced on the substrates in different ways, depending on their hydrophobic or hydrophilic characteristics.It has been possible to furnish such complex devices as hollow fibre oxygenators, tubing sets and cannulas with the heparin surface. Heparinized oxygenators have successfully been used in vivo and clinically without and/or with limited systemic heparinization.
ANTITHROMBIN III BINDING TO IMMOBILIZED HEPARIN FRAGMENTS AND ITS RELATION TO F XA INHIBITION
Authors: Kodama K , Larm O , Olsson P , Pasehe B , Risenfeldt J , Swedenborg J 
Published: August 2018

Covalent end-point attachment of heparin fragments (8 000 daltons) to artitifical materials results as published before in a highly thromboresistant surface. Approximately one out of six bonded fragments carry the antithrombin III (AT) binding sequence. i.e. the high affinity site. With regard to thrombin inhibition the heparin surface resembles the endothelium. The present work deals with the uptake on the immobilized heparin and its significance for F Xa inhibition. The uptake of AT was studied at 0.15 M and 0.35 M NaCl concentration (TRIS buffer, pH 7.4) respectively and determined as disappearance of AT activity in the exposed solutions. Large amounts were adsorbed at 0.15 M and the uptake was both concentration and time dependent. At 0.35 M the uptake was the same at all the tested AT concentrations: 5 pico-moles/square cm. It was deduced that mainly high affinity sites had taken up AT at 0.35 M and that both high and low affinity sites had taken up AT at 0.15 M.The non-AT-adsorbed heparin surface did not induce inhibition of F Xa (in TRIS buffer solution) after exposure. The surface AT-adsorbed at 0.15 M induced F Xa inhibition with the same rate in several consecutive exposed aliquots. The surface AT-adsorbed at 0.35 M had a lower inhibitory capacity and only the first F Xa aliquot was inhibited at the same rate as on the surface AT-adsorbed at 0.15 M. The inhibition rate for a second aliquot was slowlier due to the facts that AT had been consumed and that the density of AT on high affinity sites had decreased. It is concluded that AT on high affinity sites determines the rate at which F Xa is inhibited whereas the amount of AT on low affinity sites determines the inhibitory capacity by continously providing the high affinity sites with AT. The migration of AT must take place horizontally in the 100-200 A thick surface layer and may mimic events happening on a cellular membrane with binding sites of different classes for a substance.
THE EARLY THROMBOGENICITY OF IMPREGNATED DACRON GRAFTS ASSESSED IN AN ARTIFICIAL CIRCULATION
Authors: Bibby S R , Crow M J , Puri S R , Sheehan S J , Rajah S M , Kester R C 
Published: August 2018

The impregnation of knitted Dacron grafts with biodegradable protein removes the need for preclotting at implantation. The effect of such impregnation on the thrombogenic potential of these prostheses is, however, unknown. We have compared the early thrombogenicity of two impregnated knitted Dacron grafts - Hemashield ( collagen-impregnated Dacron, Meadox) and Gelseal (gelatin-impregnated Dacron, Vascutek) -with conventionally preclotted knitted Dacron in an artificial circulation. Fresh, heparinised human blood, containing 111Indium-labelled platelets, was circulated around identical twin circuits of silicone tubing by a Sarns roller pump at 180 ml/min and 120 mmHg. Into each circuit a different 15 cm × 8 mm type of graft material was mounted. Changes in platelet count, platelet aggregation to collagen, plasma haemoglobin and blood radioactivity were recorded and after 60 minutes of perfusion each graft was sectioned and counted for radioactivity prior to scanning electron microscopy (SEM) of the luminal surface. The mean graft radioactivity divided by the mean blood radioactivity yields a Graft Activity Index (GAI) allowing comparison of platelet deposition and thus thrombogenicity.RESULTS: (mean ± s.e.m.) 8 examples of each graftSEM confirmed these findings with preclotted Dacron having the highest platelet deposition. Both impregnated grafts produced significant early haemolysis within 4 minutes of blood contact. Our findings indicate that the early thrombogenicity of these impregnated grafts is significantly less than conventionally preclotted Dacron, (p< 0.01, Wilcoxon signed rank test), despite the early haemolytic phenomenon and that Hemashield grafts are less thrombogenic than Gelseal grafts. (p<0.05, Wilcoxon signed rank test)
EVIDENCE FOR AN INCREASED FIBRONECTIN SYNTHESIS IN VASCULAR ENDOTHELIUM OF DIABETIC SUBJECTS
Authors: Musso R , Longo A , Morrone M L , Cacciola R R , Lombardo A , Giustolisi R 
Published: August 2018

Increased plasma levels of Fibronectin (Fn),a well known adesive glycoprotein synthesized in vessel endothelial cells, have been reported in diabetes mellitus (DM). Previously, we provided evidence that in type II DM an elevated storage of Fn is present in endothelial cells. We here report that in diabetic subjects an abnormal synthesis of Fn in endothelial cells could also occur. To verify this hypothesis, in 15 patients affected by type II DM, age ranging 36-59, of both sex, without overt clinical vascular complications and in glycometabolic compensation (Hb Alc 8.9 ± 1.5) we evaluated before and after venostasis repeated at several times 30, 60, 90,180 and 210 min the Fn plasma levels. Five healthy volunteers, age and sex comparaf-h ble, were utilized as normal controls. The venostasis were performed at forearm pressure of 10 mmHg over diastolic x 20 min and blood samples were collected from the same vein at the intervals above indicated. Plasma Fn was evaluated by ELISA immuno-enzymatic tecnique using a commercial kit (Biochemia, Milan). The diabetic patients showed after the first venostasis a significant (p<0.001) increase of Fn (317 ± 103μg/ml) versus the baseline values (225±79 μg/ml)while normal controls did not (before 103 ± 37, after 139±61). Such an increase was also seen in EM after the second venostasis ( 298 ±91 μg/ml, vs 128±58 in controls), whereas at third venostasis plasma Fn levels retoumed to the values comparable to the basal ones both in diabetics (245 ±. 88 μg/ml) and in controls (93±41 μg/ml). After 90 min pause by performing the fourth venostasis we observed in diabetics a further increase pf Fn (298±131μg/ml) which reached:again the values noted after the first. No change, on the contrary,was found in the normal group (95±21). In the last venostasis,carried out 30min from the fourth, the plasna Fn lasted significantly (p<0.001.) increased in diabetics (281±107 μg/ml) respect to normal controls (102±19 μg/ml).Our data, therefore, would suggest that in vascular endothelium cf type II DM an increased synthesis of Fn occurs as well.
THROMBOSIS RISK FACTORS IN CARDIOVASCULAR SURGERY IN CHILDREN AND ADULTS
Authors: Philapitsch A , Ponov S , Kirchhoff P G , Urban E , Anderle K , Hrdinka R 
Published: August 2018

Antithrombin III (AT-III) and protein C (PC) deficiencies are knoi/n to be associated v/ith a major risk of thrombosis. Before, during and after cardiovascular surgery (CS) AT-III end PC were investigated in plasma samples obtained within the framework of a randomised Cl-esterase inhibitor (Cl-INH)-c.pro-tinin-placebo study in adults undergoing extracornoreel circulation (ECC), and children subjected to ECC and treated with aprotinin. Determination of AT-III and PC activity gave the following results:AT-III: Preoperative values in adults (n = 25) and children (r: = 11) were normal amounting to a median of 92 % and 10C %, res; actively. In adults a steady decrease in AT-III without any difference between the 3 groups occurred durinc ECC rntil the 1st postoperative (po) day where AT-III had faller: to CC % (median). In children the same decrease was observed duri;r ECC, however, after termination of ECC AT-III increased until normal on the 1st day po (median = 85 %) and this difference between adults and children is significant at a p of 0.019.Protein C: Median preoperative values in adults (n = 45) were 111 %, while in children (n = 11) only 48 % were found. During and after surgery in children there was no change in PC, while significant differences were found between the 3 adult groups. In the placebo group and the aprotinin group PC fell to 69 % (median) and 86 % (median), respectively, on the 1st day po. However, in the group receiving CI-INH Concentrate (Immeno) PC increased up to 136 % and only after discontinuation of treat; a-r.t decreased to 92 % (median). The significant rise in PC ir. the CI-INH group is explained by the content of PC in the CI-IMII Concentrate. These findings are indicative of a significant difference in the behaviour of AT-III and PC in children and adults, and suggest that the administration of CI-INH Concentrate may reduce the risk of thrombosis associated with ECC.
TWO-SIDE IMMUNOASSAYS OF ENZYME-INHIBITOR COMPLEXES FOR THE DIAGNOSIS OF THROMBOPHILIC STATES
Authors: Bleyl H 
Published: August 2018

The diagnosis of prethrombotic states requires methods which detect products of intravasal activation of the coagulation cascade.Two-side immunoassays for antithrombin complexes with clotting factors were developed (IXi-AT, Xi-AT, IIi- AT). These sandwich assays permit the diagnosis of hypercoagulability in the presence or absence of heparin. The biological half live time of the thrombin-antithrombin-complex was found to be about 15 min. Healthy young men 20-25 years old (n=30) have a thrombin-antithrombin-complex concentration of 0.4 ± 0.2 mU/ml thrombin equivalent (S 2238). Patients with acute myocardial infarction (n=40) showed at the time of admission to the hospital up to 10-fold (n=14), up to 100-fold (n=13) more than 100-fold (n=13) elevated thrombin-antithrombin-complex concentrations. Patients with gastrointestinal cancer showed sometime excessive elevated enzyme-inhibitor complexes.No correlation was found between thromboplastine time (Quick) and complex concentration in patients under anticoagulant therapy with dicumarole. In patients under dialysis as well as in patients under open heart surgery with extracorporal circulation, the biocompatibility can be monitored by inhibitor complex measurement.
REDUCED FIBRINOLYTIC POTENTIAL IN PATIENTS WITH ARTERIAL OCCLUSIVE DISEASE (AOD) IN COMPARISON WITH NORMAL SUBJECTS
Authors: Hartl D , Tiso E , Anderle K , Philapitsch A , Anger G 
Published: August 2018

When combining angioplasty and local lysis with urokinase (UK) in treatment of peripheral arterial occlusions we have observed marked differences in the individual patient's response irrespective of the age of the thrombus. The extensive arteriosclerotic changes revealed by angioghraphy in some of these patients suggest a reduced fibrinolytic potential depending on the underlying disease.In the standard in vitro test system we measured the UK-dependent thrombolysis in blood samples from 10 normal controls at UK concentrations of 150, 200, and 300 IU/ml of whole blood. In comparison we determined the whole blood thrombolysis time (WBTT) of 10 patients with A0D using UK concentrations of 150, 200, and 300 IU/ml of whole blood. The mean WBTT values for normal controls obtained at UK concentrations of 150 IU/ml, 200 IU/ml, and 300 IU/ml, respectively, amounted to S.5, 5.5, and 3.5 minutes, respectively, while in patients mean values of 20.7, 8.1, and 5.5 minutes, respectively, were found.Studies on plasma samples had shown that the lysis time could be shortened in a dose-dependent manner by addition of lys-plasminogen and to some extent also glu-plasminogen. Since lys-plasminogen gave clearly superior results we tried to improve the lytic potential in terms of a shortening of the WBTT by adding different doses of lys-plasminogen (0.14 - 0.56 CU/ml whole blood) to each patient sample. Although the individual response varied, the addition of lys-plasminogen to the patient samples resulted in a clear dose-dependent improvement of pathologically Pronged lysis times. We conclude from these in vitro findings that the failure of fibrinolytic therapy may in some cases be due to a reduced lytic potential, which may be enhanced Dy administration of lys-plasminogen, even when the plasminoqen level is normal.
DIURNAL FTRRINOLYTIC RHYTHM IN PATIENTS WITH FIXED HEART RATE
Authors: Peternel P , Možina H , Pušnar S , Keber D , Stegnar M , Vene N 
Published: August 2018

It has been established that fibrinolytic activity fluctuates during the day. Diurnal rhythm is possibly related to hemodynamic changes caused by daily activities. This presumption was tested in 10 patients with pacemaker and therefore fixed heart rate and limited changes in heart minute volume. Ten age and sex matched volunteers with normal heart rate served as controls. Venous blood was sampled at 8 a.m., noon, 4 p.m., 8 p.m., midnight and 4 a.m. Fibrinolytic activity was measured by three methods: spectrophotometric assay for tissue plasminogen activator (t-PA) activity, with euglobulin clot lysis time (ECLT) and on fibrin plates (FP). In patients with fixed heart rate no significant diurnal fluctuation in fibrinolytic activity was observed. In subjects with normal heart rate, diurnal rhythm was confirmed by all three methods. The highest fluctuation in activity was observed by t-PA assay with peak activity at noon (80 fold increase compared to midnight value). Also FP showed the highest activity at noon.With ECLT highest activity was detected at 4 p.m.Absence of diurnal rhythm in patients with fixed heart rate suggested importance of heart minute volume in regulation of blood fibrinolytic activity.