bluuebunny/crossref_metadata_2025_split huggingface dataset:
FIVE-YEAR-FOLLOW-UP OF PATIENTS WITH UNSTABLE ANGINA: SURGICAL VERSUS MEDICAL TREATMENT
Authors: Nellessen U , Jost S , Hecker H , Specht S , Danciu V , Lichtlen P R 
Published: August 2018

Among patients (pts) with coronary artery disease those with symptoms of an unstable angina pectoris form a subset particularly jeopardized with regard to threatening myocardial infarction (MI) or cardiac death (CD). We analyzed over 5.4±2.1 years (Y) the clinical course of 123 pts, who between 1977 and 1982 had to be admitted to the intensive care unit for reasons of persisting angina at rest. Within the first 24 hours no patient revealed a significant elevation of serum creatine kinase or typical alterations in the ECG due to acute MI (new Q-waves). During their stay in hospital (19±17 days) 43 pts (37 men, 6 women; age 58±7 Y) were subjected to bypass graft surgery, 80 pts (60 men, 20 women; age 58jh10 Y) were medically treated, 13 of whom underwent subsequent bypass graft surgery because of aggravation of symptoms. The table presents a survey of cardiac mortality and incidence of MI in the collectives with medical and surgical treatment during the stay in hospital and 1, 3 and 5 Y after dismissal (calculated according to the life-table method of Kaplan-Meier).Hence, during the initial hospitalization infarction and mortality rate in the medically treated group indeed were smaller than in the surgical collective; however, after dismissal this beneficial mortality rate turned into the opposite in the course of the following years. In this group nearly every MI was fatal.
PLATELET REACTIVITY AND FIBRINOGEN LEVELS IN UNSTABLE CORONARY ARTERY DISEASE(UCAD)
Authors: Swahn E , von Schenck H , Wallentin L 
Published: August 2018

Unstable angina and non-Q-wave myocardial infarction represents the unstable phase Of coronary artery disease (CAD). In UCAD a thrombosis in a coronary artery could be the triggering factor of the unstable phase. Increased platelet reactivity and hypercoagulability could be the predisposing factor for developing this condition. Therefore, in patients with UCAD the platelet reactivity was measured as the aggregation response to ADP and collagen, the platelet sensitivity to PgI2 and the release of platelet derived proteins. As an indicator of hypercoagulability the fibrinogen level in plasma was analysed. The control group consisted of patients with chest pain but without CAD. Blood samples for platelet tests and fibrinogen analysis were obtained in the acute phase and after one year.Results.: The only difference in platelet reactivity between cases and controls was noted in their sensitivity to PgI2. The difference remained in the females but not in the male UCAD group after one year.In the acute phase a diagnosis of UCAD, elevated weight index and smoking contributed independently to increased fibrinogen levels.Conclusion: The increased fibrinogen level and decreased platelet sensitivity to PgI2 might reflect a hypercoagulable state in patients with UCAD.
ANALYSIS OF HYPERCOAGULABILITY BY AUTOMATED FLUOROGENIC METHODS
Authors: Kato H , Uchida K , Okada Y , Yamaguchi T 
Published: August 2018

In order to detect hypercoagulable state due to the increase or decrease of coagulation factors and inhibitors concentrations or the presence of active coagulation factors or tissue factor in plasma, highly sensitive automated methods were developed using fluorogenic substrate for thrombin. Coagulability of human plasma was measured by mixing 3 yl of plasma with Thromborel S (TF), calcium and Boc-Val-Pro-Arg-MCA(MCA) (Fluorogenic PT, FPT). FPT of normal plasma was shortened by the addition of purified X or VII (Final conc. 1-5 U per ml), and of thrombin (0.3-1 ng) or Xa (10500 pg). Factors VII and X contents in plasma were measured by mixing 3 yl of diluted plasma with each factor deficient plasma, TF, calcium and MCA in which 10 %-800 % of each factor was quantitatively measured. TF and Xa were measured by mixing with XII or X deficient plasma, phospholipid, calcium and MCA. By this method, 5-500 pg of Xa or 1-1000 units of TF (assuming that one vial of Thromborel S contains 2,000,000 U TF per ml) was quantitatively measured. All the experiments were performed using a centrifugal autoanalyzer (Cobas Bio) with FIA module. The reaction time to reach 0.1 relative fluorescence was calculated by a computer using a program developed by us.These automated methods were applied to examine the hypercoagulability of plasmas from patients with cerebral infarction. Sixty five samples out of 75 showed shorter FPT than control plasma. Xa was detected with the conc. of 3-13 ng Xa per ml. FPT of patient plasmas correlated with Xa content (r=0.70) and X (r=0.63). Xa activity of patient plasma was eluted in the same peak as purified X on gel-filtration of Sephacryl S-200 column and completely inhibited by anti X rabbit IgG. Xa activity was also found in normal serum. The conventional PT or chromogenic PT methods are sensitive to hypocoagulable state but not to hypercoagulab le state. The present automated methods were proved to be sensitive to hypercoagulable state and demonstrated that the presence of Xa or the increase of X concentration in plasma contributes in part to the hypercoagulable state of cerebral infarction.
FIRST EXPERIENCE WITH A NEW SYSTEM TO MEASURE PRIMARY HEMOSTASIS IN VITRO
Authors: Zekert F , Hufnagl A , Hufnagl A , Kratzer M A A 
Published: August 2018

Control of hemostatic parameters of patients undergoing surgery usually involves only determination of parameters of the coagulation cascade, but not measurement of primary hemostasis. This has mainly methodological reasons. Recently a model of primary hemostasis has been introduced (Kratzer & Bom, Haemostasis 15:357; 1985) now produced under the name “ Thrombostat 4000” (VDG von der Goltz, 8221 Seeon, West Germany). This device measures computerized within minutes “ in vitro” bleeding parameters (vBP) like bleeding volume (V,ul), time (T,sec) and the viscosity depending initial flow (IF,ul/min) in a small sample (0.5-lml) of whole anticoagulated blood (Na citrate 1 to 10). The clinical relevance of the vBP was tested in patients undergoing major surgery.Results : Case 1: A 78 years old woman with osteomyelosarcoma, heavy bleeding and normal coagulation parametrs showed strongly pathological vBP: (V > 800, T > 300, IF 184); control values: (V = 177, T = 105, IF = 145); An improvement of beeding and shortening of vBP was observed after infusion of platelet concentrate: (V = 328, T = 245, IF = 147).Case 2: A 60 years old man with adenocarcinoma undergoing liver transplantation, before operation (OP) vBP: (V = 224, T = 114, IF = 182); displayed a strong increase during OP: (V > 800, T = 360, IF = 277; decreasing values after Oft (V = 348, T = 146, IF = 254); 1. day after OP: (V = 250, T = 127, IF = 221); 13 day after OP normal vBft (V = 160, T = 111, IF 182).Case 3: A 35 years old man with III. grade burnings of the skin (35%) and a massive platelet function defect: (V > 800, T > 180, IF = 328); improvement after infusion of platelet concentrate: (V = 393, T = 164, IF = 239); further improvement some hours later: (V = 240, T = 120, IF = 213); and normalizing of parameters at the 1. day: (V = 197, T = 126, IF = 186) and the 5. day after OP: (V = 130, T = 122, IF = 142).It is interesting to note that patients with heavy burnings reguarly displayed reduced vBP: (V = 120, T = 70, IF = 127) if measured very early after the accident. The new method seems to be a valuable instrument to judge platelet functions.
IS D. DIMERS DOSAGE USEFUL FOR DIAGNOSIS OF PRETHROMBOTIC STATE DURING POST-OPERATIVE PERIOD ?
Authors: Le Querrec A , Derlon A , Thomas M 
Published: August 2018

62 patients were at random blindly given either Kabi 2165 or commercial heparin for 6 days in prophylaxis of post-operative DVT after abdominal surgery. The radiofibrinogen uptake test (FRUT) was performed every two days during 6 days. D. Dimers quantification was performed with an enzyme—linked immunosorbent assay using monoclonal antibodies : ELISA (Diagnostics Stago). D. Dimers quantification allowed us to share out patients amongst two groups :1) Mild abdominal surgery,2) Oncologic surgery.In both groups, no difference was observed according to the treatment (p> 0.5) We saw a significant rise of D. Dimers from D-l to D6 (p< 10-6) in both groups, with significantly upper values in group 2 (p< 0.01).Among 62 patients, 3 had positive RFUT. There was no significant difference between D. Dimers values of these 3 patients and D. Dimers values of the 59 patients with negative RFUT.Thus, the rise of D. Dimers during post—operative period was not associated with DVT in these 59 patients.
PLASMINOGEN ACTIVATOR ACTIVITY OF NORMAL AND MALIGNANT MONONUCLEAR HUMAN CELLS
Authors: Filippi J F , Arnoux D , Tubiana N , Boutière B , Le Caär F , Sampol J , Hématol Lab , Sampol Pr J , Carcassonne Pr Y 
Published: August 2018

Plasminogen activators (PA) are thought to play a role in the invasive and metastatic properties of many types of cancer cells. Though, discrepancies in correlations between fibrinolytic activity and metastatic potential of malignant cells have been described.In this study, we evaluated both tissue type (tPA) and urokinase type (UK) cellular PA activities in different mononuclear cell types : normal T and B human peripheral lymphocytes, B cells from patients with chronic lymphocytic leukemia (CLL), human blood monocytes, alveolar macrophages, U 937, RAJI and JM cell 1ines.Mononuclear cells were isolated by Ficoll-hypaque gradients and monocytes by plastic adhesion. T and B cells were separated by a rosetting technique using sheep red blood cells. Cellular extracts were prepared by 0.5 % Triton X 100 buffer treatment followed by sonication and centrifugation 10 ' at 2000 g. PA assays were performed on the supernatants.UK-type PA was evaluated by a liquid-phase assay in presence of human plasminogen (Kabi) and chromogenic substrate S 2251 (Kabi).tPA was determinated using a solid-phase fibrin activity assay which involves an affinity separation step and thus allows selective detection of tPA.In both cases, results were reported in international units by reference to standard curves of UK (Choay) or tPA (Kabi).In all cell types tested, PA detected was essentially urokinase-type. Highest PA activity was found in U 937 cells (0.7 IU/5×l06 cells). In normal blood lymphocytes, mean PA activity was 0.08 IU/5×l06 cells. Examination of lymphocytes from patients with CLL revealed a marked decrease in UK activity as compared to normals (< 0.01 IU/5×106 cells in more than 50 % cases).The function of PA in normal lymphocyte physiology and the potential pathogenic role of diminished PA in CLL lymphocytes remains to be investigated.
PHARMACOKINETICS OF EN0XAPARIN AFTER SINGLE SUBCUTANEOUS ADMINISTRATION OF INCREASING DOSES (20 UP TO 80 MG) TO HEALTHY VOLUNTEERS
Authors: Bara L , Le Roux Y , Woler M , Chauliac F , Frydman A , Samama M 
Published: August 2018

The pharmacokinetics of enoxaparin (E) was randomly studied in 12 healthy male volunteers. Each dose (20-40-60 and 80 mg) was injected via subcutaneous (sc) route with a one-week wash out period. Anti-Xa and anti-IIa activities (ACT), calcium thrombin time (CTT) and Heptest were measured over a 36 hour period. E and the IV th International Heparin Standard were both used as internal standards.The anti IIa and CTT effects were only measurable when the injected dose was higher than 40 mg. The maximum anti-Xa and anti-IIa ACT were obtained 3 to 4 hours after the dose. As anti-IIa ACT is lower than anti-Xa ACT (anti-Xa/anti-IIa ACT ration I .6 to 2), the complete pharmacokinetic description of E was only based on anti-Xa data. Thus, the mean values of the maximal anti-Xa ACT (A max) were respectively: 1.58 ± 0.35 pg/ml; 3.83 ± 0.98 jig/ml, 5.38 ± 0.75 ug/ml and 7.44 ± 1.4 pg/ml for the four doses (20-40-60 and 80 mg). The resorption of E after sc injection was strictly linear whereas the relationships between A max or AUC in the one hand and dose in the other hand were A (anti Xa) Max = 0.0954 (dose) - 0,2083 r = 0.9146/p < 0.001; n = 48) and AUC (0 - 36 h) = 0.9117 (dose) - 7.59 (r = 0.9133/p < 0.001; n = 48). The mean residence time of E was close to 6 h (5.83 ± 0.86 h for D = 40 mg; 6.19 ± 0.74 h for D = 60 mg and 6.44 ± 0.76 h for 80 mg) indicating that around 50% of the total anti Xa ACT is induced in a 6 hour interval. The apparent volume of distribution V is close to 61 (6.59 1 ±1.33 1 for D = 60 mg) and the total Dody clearance is equal to 1.25 1/h, indicating the rate of depolymerisation of enoxaparin is lower than that of heparin. Plasma elimination half-life of anti-Xa ACT is equal to 4.36 ± 1.07 h (D = 40 mg) whereas that of anti-IIa ACT is shorter, fi) = 2.1 h). These results indicate that enoxaparin exhibits i) a differential anti-Xa/anti-IIa ACT profile, ii) a linear relationship between dose and anti-Xa/anti-IIa ACT and iii) a kinetic profile which is significantly different from that of standard heparin.
TOLERANCE OF CY 216 AS THROMBO-EMBOLIC DISEASE PREVENTION : EVALUATION OF LOCAL HAEMORRHAGIC RISK IN OPHTAL SURGERY - Preliminary results
Authors: Morin Y , Limon S 
Published: August 2018

The specific biological activity of low-molecular weight heparin prompted using CY 216 in ophtalmological surgery for thrombo-embolic prevention. We report preliminary results on 31 patients (9 males, 22 females, mean age 74,4) treated from 06/86 to 12/86 with a daily 0,3 ml sub-cutaneous injection of CY 216 started 2 hours prior to surgery until day 7, or day 10 for 7 patients. Coagulation tests included TCa and anti-Xa activity. All patients were checked daily for ocular haemorrnagies and thrombo-embolic manifestations. Anaesthesia was general in 16 cases and local in 15. Surgery was performed on 21 cataracts (67 %), 8 retinal detachments (26 %), 2 glaucomas (6 %).No patient developped any clinical thrombo-embolism condition. In that particular surgery where frequent local haemorrhagic complications occur and delay the onset of heparinotherapy, CY 216 treatment exhibited 3 minor eyelids ecchymosis, 1 choroid hematoma and 5 subconjonctival suffusions, all transient and not impacting specific surgical results ; and all already known as possible mechanical vascular aggression independant of heparinotherapy. 2 hyphemas (6 %) also occured, for which CY 216 was discontinued, still not impacting surgical results, and without excessive hypocoagulation according to tests. These biological tests showed no adverse effects ; TCa never raised more than 6" above controls, and anti-Xa activity raised to 4 times pre-treatment values ; in 3 patients, high values did not induce any haemorrhagic complications, a very strong argument in favor of excellent tolerance of CY 216 therapy.At this stage of preliminary results, the tolerance of CY 216 concerning local haemorrhagic risk in eye surgery can be evaluated as near to excellent.
PREVENTION OF CORONARY VEIN GRAFT OCCLUSION: LOW-DOSE ACETYLSALICYLIC ACID VERSUS COUMARIN (ASAAC - STUDY)
Authors: Weber M A J , Taillens C , Hasford J , Spannagel M , Schramm W , Hauf E ,   ASAAC - Study Group
Published: August 2018

Thrombotic graft occlusion occurs within a few hours after surgery, suggesting a benefit of preoperative start of antiplatelet treatment. We investigated the effectivity and risk of preoperatively started treatment with 100 mg/day acetyl salicylic acid (ASA) compared to anticoagu1 ation started 6 hours postoperatively (heparin followed by coumarin (AC)). The prospective randomized trial yielded the following results:Preoperative low dose ASA increased chest-tube blood loss. This indicates effective antiplatelet activity of low dose ASA. Perioperative platelet consumption and coagulation factors activity was not altered.It is concluded, that graft patency rates are similar with postoperative anticoagu1 ation or antiplatelet treatment with low dose acetylsalicylic acid.
MODEL STUDIES OF NEUTRALIZATION OF THROMBIN
Authors: Reeve E B 
Published: August 2018

A kinetic model, based on published studies of thrombin neutralization, is used to examine factors that limit spread of free thrombin in a simple plasma. It employs equations with presently available rate parameters which describe the courses of the major thrombin-binding reactions at 37°C in buffered saline solutions approximating plasma ultrafiltrate. Thrombin is bound reversibly by fibrinogen and fibrin-1 polymers as enzyme-substrate complexes (1) and by “fibrin” at a non-proteolyt ic site (2), and essentially irreversibly by antithrombins (3). These bindings reduce free thrombin levels and so limit spread of activity. The model equations with parameters from (1) and (3) show that thrombin neutralization by thrombin-substrate complexes is very brief and thrombin-antithrombin reactions are much too slow for early reduction of thrombin activity. However, parameters from (2) show that rapid reversible binding of thrombin by “fibrin” much reduces level of free thrombin and the level continues to fall as the thrombin is passed to the antithrombins. The model shows that a rapidly-acting antithrombin (e.g. heparin-ATIII) could reduce free thrombin fast enough to inhibit slower thrombin activations (e.g. of FXIII), and that a sufficient concentration of a reversible binder can govern the level of free thrombin. This suggests that a non-toxic reversible binder, with suitable Kd and half-life, would be valuable in treating thrombosis. Verification and extension of the model findings require better experimental definition of the parameters.(1) Lewis, S.D. et al. J. Biol. Chem. 260, 10192-10199, 1985.(2) Liu, C.Y. et al. J. Biol. Chem. 254, 10421-10425, 1979.(3) Jordan, R. et al. J. Biol. Chem. 254, 2902-2913, 1979. (Supported by grants from the Colorado Heart Foundation)
EFFECT OF NICOTINE ON HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS IN CULTURE : PROSTACYCLIN PRODUCTION AND PROLIFERATION STUDIES
Authors: BOUTHERIN-FALSON O , BLAES N 
Published: August 2018

Clinical observations and results from animal studies indicate that nicotine may play a role in vascular disorders related to smoking. It has been reported that nicotine could alter vascular prostacyclin (PGI2) production and increase the number of circulating endothelial cells. In the present study, the direct effect of nicotine on endothelial cells in culture was investigated : Both PGI2 production and proliferative abilities were studied.PGI2 production studies : human umbilical vein endothelial cells (HUVEC) were grown in 4 days to confluency in control medium (RPM/199 1:1 + 20% fetal calf serum). At the beginning of the experiments, medium was replaced by tyrode Hepes buffer added or not with nicotine at different concentrations (0.05,0.5, 5, 50 or 200 ug/ml). Basal production of PGI2, assessed after 20 minutes, was significantly increased by 0.5 ug/ml nicotine (223% of control) ; subsequently thrombin (1 U/ml) stimulated release was measured after 5 minutes, it was dose dependently decreased by nicotine. Thus, at least in basal conditions, nicotine treatment of HUVEC alone in culture did not permit us to reproduce the inhibitory effects described on models involving smooth muscle cells in addition to the endothelial cells. Otherwise, nicotine could interfere with stimulating agents such as thrombin. Investigations on the effect of these agents in combination are currently in progressProliferation studies : Cells were grown in nicotine or control medium. Proliferation ability, estimated by the increase in cell number at daily interval was slighly increased in cultures receiving 0.05 ug/ml nicotine (110.4% of control). This tendancy was confirmed by 3H Thymidine incorporation (+41%). On the contrary a decrease in cell density was observed for the highest concentrations, from 50 ug/ml. This later effect did not seem to be related to any cytotoxicity or cell detachment. Thus, endothelial cells appeared to be highly responsive to nicotine in their PGI2 production while their growth characteristics were rather resistant to nicotine treatment.
DIETARY LIPIDS, INFECTION AND MACROPHAGE PROCOAGULANT ACTIVITY
Authors: van Dam-Mieras M C E , Muller A D , Hornstra G 
Published: August 2018

It is generally accepted that the type of dietary fat influences arterial thrombosis and atherosclerosis. Although it is still largely unknown how the dietary lipid composition influences the process of atherogenesis, it is evident that several cell types are involved. Morphological evidence for the involvement of monocyte/macropages has been given.We described before that the dietary lipid composition has striking effects on the procoagulant activity of macrophages. When macrophages were isolated from the spleens of healthy rats the procoagulant activity slightly decreased during the first few hours after isolation, and reached a plateau value after 4 hours. When, however, macrophages were obtained from animals infected with a pneumona virus (PVM) different results were obtained:Experiments carried out with peripheral blood monocytes showed close resemblance to those described in the table.These results show that:- moncytes/macrophages isolated from PVM-infected animals increase their procoagulant activity during in vitro culture- the differences in macrophage procoagulant activity found in cells obtained from healthy animals fed diets containing different lipids no longer were found in PVM-infected animalsThis would implicate that the infection process has a more profound influence on macrophage procoagulant activity that the composition of the diet
MODULATION OF THROMBIN-MEDIATED REACTIONS IN HAEMOSTASIS- BY TREQUINSIN AND ITS ANALOGUES.
Authors: Blasko Gy , Blasko G , Sas G , Szantay Cs 
Published: August 2018

A new pyrimido/6,1-a/-isoquinoline derivative ,/Ref.1 / developed by Hoechst and named Trequinsine has been reported to be a powerful inhibitor of cAMP phosphodiesterase and platelet aggregation having a potency nearly similar to prostacyclin. We synthesized Trequins-in (1), its indole derivative (4) , as well as their precursors (2 3) and subjected them to a study in order to evaluate their effects on haemostasis. Surprisingly they exhibited a modulatory effect only on reactions mediated mainly by thrombin. They inhibited platelet aggregation (ICc:q for Trequinsin: 13 + 2.5 ng/ml, for indole derivatives: 1-3 /ig/ml); 1, 2, 4 enhanced the amidolytic activity of CC-thrombin towards S-2238 substrate within a narrow range of submicromolar concentrations but they did not exert any effect on the activity or the inactivation of Factor Xa and plasmin.Compound 2 proved to be an inhibitor of prostacyclin production of rat aortic tissue (Trequinsin has much less effect) but in contrary to this 3. and 4 exerted an enhancing effect on the total prostacyclin production.