bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antithrombotic Effect of Acetylsalicylic Acid. Heparin and Phenprocoumon in Experimental Thrombosis
Authors: Barth P. , Zimmermann B. , Zieboll J. , Lange D.
Published: June 2019

The effect of acetylsalicylic acid (ASS) was studied in 450 experiments using 250 rabbits in which thrombus formation by endothelial lesions, hypercoagulability and stasis was standardized and induced to various degrees of severity. The effects of ASS were compared with those of heparin and phenprocoumon singly and in combination with ASS. In the first series of experiments in 120 rabbits stasis thrombi were induced according to Wessler modified by application of purified contact activation product (CAP). Thrombus formation in the jugular vein was most marked inhibited by heparin (significantly). ASS alone was ineffective. In a second series of experiments endothelial lesions were produced in 80 rabbits in the jugular vein by freezing. 15 min later, CAP was administered in low doses and stasis was produced. Measurement of thrombus size was by gravimetry. Moderate effect of ASS. The inhibitory effects on thrombus size of heparin, phenprocoumon and phenprocoumon in combination with ASS were significant. In a third group of 50 rabbits endothelial lesions were produced in the jugular vein and carotid artery by applying a solution of silver nitrate. Thrombus size was determined by measuring the activity of Cr51 labeled red cells and J125 fibrinogen in the thrombosed vascular areas. Significant effects were observed with ASS and with heparin. Discrepancies between the two methods (Cr51 and J125) used to measure thrombus size are discussed. Comment: Even if endothelial lesions are the predominant causes for thrombus formation, heparin is as effective as ASS in these studies (group 3). If thrombosis is produced by all thrombogenic factors ASS appears to be effective, however without statistical significance (group 2).
Physicochemical Studies on Artificial Surface/Protein/Platelet Interactions
Authors: Nyilas E. , Chiu T.-H. , Morton W. A. , Lederman D. M. , Herzlinger G. A. , Cumming R.D.
Published: June 2019

To highlight the mechanisms of artificial surface/protein/platelet interactions, results obtained by various methods have been integrated to elucidate some of the correlations between phenomena which occur at the macromolecular level and subsequently influence those at the cellular level, such as platelet adhesion. Microcinematographic evidence obtained under the controlled conditions of the Stagnation Point Flow Experiment (SPFE) indicate that, even on glass, platelet adhesion commences only after 30-60 sees of exposure to native blood. This lag period is consistent with diffusion kinetics predicting the arrival of plasma proteins should overhwelmingly precede that of the cellular components. During the lag period, native plasma proteins collide with the artificial surface and, in most cases, adsorb with surface-induced conformational changes. The energy for altering the secondary protein structure is supplied by the heat of adsorption. The extent of adsorption and structural alterations depend upon both the type of protein and the molecular architecture of the artificial surface, viz., the number density and orientation of polar, H-bonding, etc. groups accessible to proteins. Using microparticulate glass (< μ dia.) and a microcalorimeter sensitive to ±0.00001° C in 100 ml of sample volume, serum albumin was found to adsorb, release heat, and desorb in a conformationally altered state. In contrast, γ-(7S)-globulin and fibrinogen underwent irreversible multilayer attachment releasing (1.0-1.7) χ 103 Kcal/mole of protein adsorbed directly to the glass surface. Proteins in the second, etc. sorbed layers released much smaller heats. The electrophoretic mobility of the same particles coated with varying amounts of the same proteins confirmed that the relatively greatest conformational change occurred in the protein layer directly attached to the artificial surface. On homologous Nylons exposed under identical hemodynamic conditions in the SPFE, the surface number density of platelets remaining adherent at points of identical shear was proportionate to the polar force contribution of those surfaces. These results indicate that the protein layer which settles first, is acting as a “proportional transformer” mediating the effects of artificial surfaces onto platelets.
Silent Venous Thrombosis Revealed by Impedance and 125I-Fibrinogen
Authors: Hume M.
Published: June 2019

100 post-operative subjects were observed following total hip replacement using 125I-fibrinogen (125I-Fg) and impedance plethysmography (IPG) with thigh cuff. Phlebo-grams were obtained if these tests indicated venous thrombosis. Also, lung scan was obtained if clinical evidence of pulmonary embolism developed. Sustained significant isotope localization occurred in 40. 32 of these had abnormal IPG. Four patients had minor pulmonary embolism, which was associated with abnormality of either 125I-Fg or IPG. All major obstructive venous thrombosis and all moderately extensive thrombosis was associated with abnormal IPG. Only minute thrombi were not correctly classified by IPG. The following conclusions are supported by this experience. 1) If prospectively applied in patients at risk, the combination of both techniques (125I-Fg, IPG) is capable of detecting all silent venous thrombosis even minute thrombi of negligible significance. 2) IPG is capable of detecting all major obstructive and all moderately extensive thrombi, that is, all thrombosis of clinical significance arising in the leg. 3) Minute thrombi will not be detected by IPG alone and small emboli resulting from detachment of such minute thrombi would be unheralded unless monitoring includes 125I-Fg.
Reduction of Platelet Survival: Development of a Thrombosis Model
Authors: Meuleman D. G.
Published: June 2019

In male Wistar rats a PT 46 cannula was inserted in the carotid artery via the aortic arch into the abdominal aorta and fixed in that position. Twenty-four hours later 51Cr-labelled blood platelets were injected into these animals and into sham operated animals.

The survival time of the 51Cr-labelled platelets in the cannulated group was significantly reduced as compared to the sham operated group. The mean half lives and s.e. mean were 15.5±1.3 hours and 30.3±0.5 hours respectively.

The distribution of radioactivity deposited in various organs three days after administration of the label was determined. In the cannulated group the kidney contained twice as much radioactivity as in the sham operated animals, the spleen contained approximately 30% less.

The number of free, single platelets was decreased in the cannulated group.

These results and the relevance of aortic cannulation for the development of a model for thrombo-embolism will be discussed.
Thrombogenicity of Human Factor IX Concentrates. In vitro Studies
Authors: Sas G. , Owen R. , Smith J. K. , Middleton S. , Cash J. D.
Published: June 2019

A series of in vitro studies, designed to ascertain the potential in vivo thrombogenicity of human factor IX containing concentrates, is described. Using concentrates obtained from several different centres the fibrinogen clotting time with some preparations was less than 6 hours and/or the recalcification time of normal plasma was shortened. In some preparations however, the plasma recalcification time was lengthened.

Further studies revealed that all diluted factor IX concentrates generated thrombin after recalcification, and that the rate of thrombin generation appeared to be characteristic of a particular preparation. This characteristic we have expressed as the TGt50 which is the incubation period in minutes required, after recalcification, to obtain a 50 second clotting time of a fibrinogen substrate. The TGt50 was found to correlate most strongly with recalcification time of celite exhausted plasma (p < 0.001), but no correlation was observed between it and the immunological factor VIII or antithrombin III levels. However some factor IX concentrates contained antithrombin III in a free (biologically active) and in a complexed (inactive) form.

Evidence is presented which suggests that the thrombin generation test and recalcification time of celite exhausted plasma may represent suitable in vitro quality control assays for the potential thrombogenicity of factor IX concentrates.
Factor IX Concentrates and Thrombosis: Amplification of Thrombotic Potential by Interaction between Material Infused and the Host
Authors: Lundblad R. L. , Kingdon H. S.
Published: June 2019

Therapeutic infusion of Factor IX concentrates have occasionally been accompanied by episodes of thrombosis, some of them fatal (Blatt et al., Ann. Int. Med. 81, 766, 1974). On this occasion there were diffuse arterial and venous thrombi; in other cases pulmonary emboli or thrombosis of the vein being infused were observed (Kasper, N. Eng. J. Med., 289, 160, 1973). Disseminated intravascular coagulation has also been reported (Ceder-baum and Roberts, Clin. Res. 21, 92, 1973). When the concentrates were dissolved according to the manufacturer’s directions, diluted serially in buffered saline, and assayed for their ability to shorten the non-activated partial thromboplastin time (PTT) of normal plasma in plastic tubes, marked shortening of the PTT was observed, demonstrating the presence of clot-promoting enzymes. When reconstituted concentrates were incubated with calcium chloride prior to assay, much more thrombogenic enzyme was detected. The untreated concentrates contained no thrombin, and much of our data now suggest that the major thrombogenic enzyme is activated Factor IX. However, the concentrate after treatment with calcium contained large amounts of thrombin, up to 350 NIH units per ml of concentrate. This demonstrated interaction between concentrates and calcium ion suggests a mechanism whereby the thrombogenic potential of the material infused could be amplified by interaction with the calcium ion in the bloodstream of the patient beino-treated.

Other experiments have shown that antithrombin III plus heparin can inhibit either the thrombogenic materials found in concentrates, or the enzymes generated de novo by prior incubation with calcium.
Prothrombin-Complex Concentrates, Thromboses, and Factor VIII Inhibitors: Evidence for a Coagulant Formed by the Interaction of Factors X and II
Authors: Tishkoff G. H.
Published: June 2019

Kurcyznski and Penner have reported on the use of prothrombin concentrates in the management of bleeding in hemophilia patients with Factor VIII inhibitor. Several commercial concentrates showed marked ability to shorten the activated partial thromboplastin time (APTT) of Factor VIII inhibitor plasma after 40 min preincubation. Significantly, purified human Factor Xa and thrombin did not evidence corrective effect. Highly purified human Factors X and II, isolated by affinity chromatography from partially activated prothrombin complex, effectively corrected the APTT when combined, but were inactive when tested separately. Preliminary studies suggest that Factor V is essential. This study indicates that the thrombogenic properties of prothrombin concentrates in vivo may be due in part to a coagulant complex formed by the interaction of X, V, and a prothrombin intermediate.
Inhibition of Thrombotic Side Effects of II, VII, IX and X Concentrates
Authors: Johnson A. J. , Macdonald V. E. , Brandt D. , Middleton S. , Smith J. K.
Published: June 2019

Well documented thrombotic side effects of II, VII, IX and X concentrates are thought to be due to spontaneous partial activation of one or more coagulation factors. Using the unactivated PTT method of Kingdon and the thrombin time as global assays of activation, we have confirmed this concept. It has been suggested that heparin should be added to the concentrate, but preparations vary in antithrombin content and activated factor. The amount of heparin for each preparation would have to be titrated in order to neutralize the activated factors without anticoagulating the patient. We sought to extend the range of added heparin without producing an anticoagulant effect, by adding heparin to the concentrates prior to use of the PEG fractionation method to remove the hepatitis antigen. Thus, heparin-activated antithrombin III can inhibit activated clotting factors while residual free heparin is removed by PEG fractionation. When 1 unit of heparin per mg of protein in the concentrate was added prior to PEG treatment, the final products from more than 80 runs on 15 batches (3 major manufacturers) were almost invariably neutral; neither anticoagulated nor activated. The thrombin clotting time, when measured, was 6-24 hours. The average yield with use of the PEG fractionation method was 85%; depending on the initial purity of the concentrate, the final product had an additional purification of 1.0-2.5 X that of the starting material.

(Supported in part by USPHS Grant HL 15596 and HRC (N.Y.) 1-681.)
Improved Factor VIII Yield in Cryoprecipitate Using a Quick Thaw Technique
Authors: Davidson J. F. , McAdam J. H. , Mackenzie M. J. , Kavanagh M. L.
Published: June 2019

Standard Cryoprecipitate was prepared from fresh citrate phosphatedextrose plasma by snap freezing at —70° C and then thawing at +4° C in air for 18 hours. In 143 experiments the yield of Factor VIII from the starting plasma was 42%.

In 64 paired experiments the Factor VIII yield in Cryoprecipitate from fresh plasma was increased, from 43% in the standard method to 56% when a quick thaw of 50 minutes at +4° C in a liquid bath was introduced. In 10 other paired experiments the yield in the standard method was raised from 51% to 61% when 90 minutes of super-cooling at —6° C in a liquid bath was introduced prior to snap freezing. When, however, the quick thaw and super-cooling modifications were combined in 42 paired experiments, the yield was only 49% compared with 42% by the standard method.

It is concluded that this simple quick thaw modification will produce a greater yield of Factor VIII in Cryoprecipitate and that the addition of the technically more demanding super-cooling modification does not give a significantly greater yield.

It seems likely that the longer period at +4° C in the standard method leads to denaturation of a proportion of the Factor VIII and loss of activity. Factor VIII antigen, however, was not lost. In a smaller number of experiments approximately all the Factor VIII was recovered in the Cryoprecipitate and its supernatant. Furthermore, the relative proportions of Factor VIII antigen and procoagulant in the Cryoprecipitate were found to vary in concert suggesting that the Factor VIII molecule is not dissociated in the process of cryoprecipitation.
A Clinical Trial of Antiplatelet Therapy in Patients with Coronary Arterial Disease
Authors: Michaels Leon , Galbraith P. A. , Ledwich J. R.
Published: June 2019

Patients who had received long-term anticoagulants for acute coronary insufficiency or myocardial infarction were followed for 16 weeks after stopping treatment. There was a 37% thromboembolic relapse rate among 82 subjects who had angina during the last 3 treatment months and/or symptomatic occlusive extra-cardiac arterial disease.13 additional patients with one or both of these features were then selected for an antiplatelet therapy trial; having received warfarin for 1 to 2 years, they were switched to a 16-week course of entrophen 300 mg and sulfinpyrazone 200 mg, 4 times daily. Treatment was monitored by platelet adhesiveness, template bleeding time and serum salicylate measurements. There were no hemorrhagic complications. In 3 patients, intolerance compelled dosage reduction or stopping one drug; 10 adhered to protocol. 4 of the 13 suffered a thromboembolism while taking both drugs according to protocol. This 31% incidence is almost identical to that seen when no treatment followed warfarin withdrawal. The study is continuing, but the results to-date suggest that entrophen-sulfinpyrazone is not a practical or effective treatment for coronary disease. They do not preclude possible effectiveness of this combination in other vascular disease or other antiplatelet drugs in coronary disease.
Factor VIII Related Antigen in Normal Blood Platelets and in Platelets of Patients with von Willebrand’s Disease
Authors: Bouma B. N. , Hordijk-Hos J. M. , Graaf S. de , Mourik J. A. van , Sixma J. J.
Published: June 2019

The presence of Factor VIII-related antigen (F VIIIRA) in haemostatic plugs was demonstrated by immunofluorescent techniques. Immunofluorescent studies of intact washed platelets incubated with rabbit antifactor VIII in suspension showed that most of the platelets did not stain, whereas a positive staining was obtained after disruption of the membranes after air-drying of a drop of the same platelet suspension on a glass slide. This suggested that F VIIIRA was localized inside the platelets. F VIIIRA was detected in the supernatant of washed platelet suspensions that had been lysed by freezing and thawing (4 ×). This platelet F VIIIRA could not be distinguished from plasma factor VIII in immuno diffusion studies and cross-immuno-electrophoresis using antinormal factor VIII and the antisera against the low ionic strength subunits of factor VIII. The concentration of F VIIIRA in normal platelets was about 60 times as high as the concentration in plasma. Normal concentrations of F VIIIRA were detected in blood platelets and in 13 out of 15 patients with Von Willebrand’s Disease. No F VIIIRA was detected in the plasma of these patients with Von Willebrand’s Disease. Blood platelet F VIIIRA of normal platelets and of platelets of patients with Von Willebrand’s Disease supported the Ristocetin aggregation of washed platelets.
C1-Inactivator as a Determining Factor in Contact Activation of Fibrinolysis
Authors: Kluft C.
Published: June 2019

The rate of contact activation of fibrinolysis is considered to reflect the activation rate of proactivator and Hageman factor. This study was undertaken to determine the role of Cl-inactivator in this process.

Contact activation of fibrinolysis was performed according to Ogston et al. (1969), J. Clin. Invest. 48, 1786-1801. The rate of activity generation was measured in plasma with various levels of Cl-inactivator and appeared to be dependent on that level; i.e., a high level of Cl-inactivator corresponds with a slow rate of activity generation.

It has recently been demonstrated that the fibrinolytic activity of euglobulin fractions is strongly inhibited by Cl-inactivator also present in this fraction. The activity generation of contact activation is found to be accompanied by a gradual decrease in functional Cl-inactivator in the euglobulin fraction. The fibrinolytic activity is set free by this disappearance of inhibition.

It is concluded that the rate of contact activation of fibrinolysis must be interpreted in terms of the inactivation of Cl-inactivator rather than of the activation of proenzymes. All enzymes capable of inactivating Cl-inactivator can contribute to the process of contact activation of fibrinolysis. This mechanism might account for the observed defects in fibrinolysis in vitro in Fletcher Factor deficient patients.
Immunoradiometric Assay of Factor VIII Related Antigen
Authors: Ruggeri Z. M. , Mannucci P. M. , Jeffcoate S. L. , Ingram G. I. C.
Published: June 2019

The development of a solid phase non-competitive immunoradiometric assay (two-site assay) has allowed us to measure factor VIII related antigen (VIIIAGN) in normal plasma diluted up to 2500 times (4.10-4 U/mg). The assay is based on the extraction of VIIIAGN from plasma by means of polystyrene tubes coated with a specific rabbit antiserum and subsequent labelling of the extracted protein with 125I labelled rabbit anti-VIIIAGNIgG. The plasma values obtained in 32 normal subjects were highly correlated with those obtained by means of rocket Immunoelectrophoresis (r = 0.94). A positive correlation was also shown with factor VIII procoagulant activity (VIIIAHF) (r = 0.61), and with von Willebrand factor (VIIIVWF) (r = 0,64). In 14 patients with severe von Willebrand’s disease (vWd), VIIIAGN was not detectable (< 4.10-1 U/ml) in 8 cases or measurable in trace amounts (6.10-4–10-2 U/ml) in 6 cases. Measurable levels could also be obtained (5.10-2–10-1 U/ml) in 14 additional cases of vWd in which VIIIAGN was below the sensitivity of the rocket Immunoelectrophoresis technique (10-1 U/ml).
Disappearance Rate ot the Anticoagulant Effect of Heparin
Authors: de Swart C.A.M. , Nijmeijer A. , Akkerman J. W. N. , Sixma J. J.
Published: June 2019

The disappearance of the anticoagulant activity of a intravenously administered well-defined commercial heparin was followed in human and dogs utilizing a diluted activated partial thromboplastin time (Marder) and an anti-Xa-assay (Tin). The anticoagulant activity was followed after the injection of a large single dose. More accurate determination of the relation between heparin level and disappearance rate was achieved by continuous infusion with different heparin dosages. The anticoagulant effect was linearly related with dosage administered above a certain minimum threshold. This is in agreement with disappearance curves obtained after a single injection that can be described by the formula:

(in which S represents the heparin activity, K1 and K2 represent constants and K3 is the integration constant).

References: Marder, V. J.: A simple technique for the measurement of plasma heparin concentration during anticoagulant therapy. Thromb. Diath. Haemorrh. 24, 230–239, 1970.

Yin, E. T., Wessler, S.: Plasma heparin: A unique, practical, submicrogram sensitive assay. J. Lab. Clin. Med. 81, 298-310, 1973.
Platelet Aggregability Measured by SFP Method in Cerebral Thrombosis and Haemorrhage
Authors: Kobayashi I. , Yamazaki H.
Published: June 2019

Platelet aggregability of 50 aged healthy people (64.0 ±9.4 yrs., Mean ±SD), 93 essential hypertension (65.6±8.5 yrs.), 166 recovery stage of cerebral thrombosis over 2 months from the onset (62.4 ± 11.8 yrs.) and 74 recovery stage of cerebral hemorrhage (57.4 ±10.0 yrs.) was measured using screen filtration pressure (SFP, Swank, 1961) method. SFP by 3 μM ADP of healthy, hypertension, recovery stage of cerebral hemorrhage and thrombosis were 148.7±53.5, 176.2± 74.4, 189.8±58.3 and 206.3±58.9 mmHg respectively. The differences of the SFP between the healthy and the diseased groups were statistically significant (P < 0.01-0.05). Meanwhile SFP of 9 cerebral thrombosis (66.8±9.5 yrs.) and 18 hemorrhage (66.4 ±10.6 yrs.) was measured during their time course of the diseases from the onset to 180 days. SFP in acute stage of thrombosis showed an increase and it decreased gradually during the time course. On the contrary SFP in acute stage of hemorrhage showed a decrease and it increased gradually. A statistically significant difference was observed between both the groups within 30 days from the onset (P < 0.01 ). SFP in acute stage of hemorrhage showed 95.2 ±17.7 in 9 survival and 1Ö4.0±Ö6.2 mmHg in 9 death cases within 10 days from the onset. The difference of the SFP between survival and death was statistically significant (P < 0.01).
Study of Haemostasis in Schoenlein-Henoch’s Syndrome
Authors: Boros Gy. , Sámik J. , Gofman Ljubov , Nagv Judit , Deák Gy. , Hámori A.
Published: June 2019

Blood coagulation, thrombocyte function and capillary resistance were studied in 21 adult patients with Schoenlein-Henoch’s syndrome. 20 different tests were carried out at different stages of the disease. In 2 cases skin, in 1 mesocolon and in 10 kidneys were examined histologicaly (light microscopy, immunofluorescence, electron microscopy).

Capillary permeability was increased at least once in every patient. All patients but 2 were characterized by hypercoagulability. In addition to thrombotic changes, an increase in labile fibrinogen was detected in the serum of 12 patients, and thrombin time was prolonged in 11 patients on 31 occasions. Plasma fibrinolytic activity was increased in 11 patients. Fibrin deposition was demonstrable in the skin of 2 in the mesocolon of 1 and in the kidneys of 7 patients.

It is suggested that besides the capillaropathy a coagulation defect, resembling consumption coagulopathy is a characteristic of Schoenlein-Henoch’s syndrome.
Abnormal Blood Yield Stress as an Aetiological Factor in Postoperative Deep Venous Thrombosis
Authors: Humphreys W. V. , Walker A. , Charlesworth D.
Published: June 2019

An elevated blood viscosity could lead to increased venous stasis and a higher incidence of post-operative deep vein thrombosis. Immediately preoperatively we have measured, using a Contraves low shear 2 viscometer, blood yield stress and viscosity at high and low shear rate in 28 general surgical patients. These patients were then screened by the standard I125 fibrinogen technique to detect the development of deep vein thrombosis post-operatively.

13 patients developed a deep vein thrombosis. These patients had a significantly higher blood yield stress, corrected to a standard haemoerit of 45%, than the others (P < 0.01 students t). All other viscosity parameters were normal in these patients. Patients with malignant disease had a very high incidence of thrombosis (90%: 30%) and significantly higher yield stress values (mean 0.26 dynes/cm2: mean 0.194 dynes/cm2, P < 0.0005 students t) compared to patients with benign disease.

We conclude that a high blood yield stress could be an important aetiological factor in thrombosis and the high values obtained in patients with malignant disease could partly explain the high incidence in these patients.
The Use of Thermography in Diagnosis of Deep Venous Thrombosis (DVT): A Comparison with Phlebography
Authors: Hallböök T. , Bergqvist D. , Dahlgren S.
Published: June 2019

None of the existing diagnostic methods for detection of DVT is ideal and thus the search for new methods is necessary. When clinical criteria were used the increased skin temperature was one of many signs, a result of the inflammatory reaction around the thrombus. With thermography it is possible to detect temperature differences of 0.2° C and there is a recent report suggesting that thermovision can be used to detect DVT (Cooke & Pilcher, Brit. J. Surg. 67, 971, 1974). Our study was made to test which thermographic signs were seen in patients with phlebographically diagnosed DVT. The patients were studied with AGA 680 medical thermographic system and the front of the calf and thigh and the back of the calf were studied. Normally there were big areas of tibial and patellar coolness and a mottled thigh appearance. Patients with DVT according to phlebography showed and increased temperature compared to the normal leg, a diminished or absent tibial and/or patellar coolness and sometimes a hot streak corresponding to the thrombus. 24 patients have hitherto been studied (unilateral phlebography). In 22 cases there is full agreement between the methods and in 2 cases the agreement is less clear. As the method is simple and the agreement good the study continues to obtain a larger clinical material.
Dispersion of Stabilized Plasma Clots Incubated in Normal Plasma or Serum by 5 M Urea
Authors: Cataldo de F. , Bando F.
Published: June 2019

Clots obtained from normal native platelet-poor plasma are dispersed by addition of 5 M urea within 120 hours. Clots from plasma diluted > : 4 (Ann. NY. Acad. Sei. 202, 341–343, 1972) and clots from undiluted plasma, thoroughly washed and incubated in veronal buffer pH 7.4, are not dispersed by urea, but they are rendered susceptible to the dispersing action of urea by prior incubation in normal undiluted plasma or serum. The same phenomenon was observed by incubating the otherwise unsoluble clots in normal plasma or serum fractions precipitated at 33% saturation with (NH4)2SO4. The plasma fraction is more active than the serum one. This fraction was tested by casein-14C putrescine Factor XIII assay: it does not interfere with the incorporation of putrescine into casein, although it conditions the urea- dispersing action on stable clots.
Platelet Membrane Glycoproteins Implicated in Ristocetin-Induced Aggregation
Authors: Jenkins C. S. P. , Phillips D. P. , Clemetson K. J. , Meyer Dominique , Larrieu Marie-José
Published: June 2019

Ristocetin induces aggregation of platelets in the presence of Willebrand Factor. Certain preparations of ristocetin when preincubated with washed normal platelets render the platelets less responsive to the addition of Willebrand Factor. It has been demonstrated that such preparations are contaminated with a proteolytic enzyme(s). Platelets treated in this way with different ristocetin preparations were analysed using disc gel electrophoresis. Membrane glycoproteins I and II were depleted only when using contaminated ristocetin preparations. Platelets labelled with 3H-adenine when treated with this ristocetin did not demonstrate leakage of 3H-labelled material, thus showing that the platelet membrane remained intact.

Platelets were treated with proteolytic enzymes of known specificities and following further washing were tested in an aggregating system consisting of ristocetin and Willebrand Factor. The aggregation response was markedly reduced compared to control platelets. These results point to the glycoproteins of the platelet membrane being part of the receptor for the ristocetin-Willebrand Factor complex.
Low Dose Heparin Versus Oral Anticoagulants in the Prevention of Postoperative Venous Thrombosis in Gynecology
Authors: Schaer A. E. , Huber L. , Bader P. , Baertschi U. , Morf P.
Published: June 2019

In a randomised trial involving 458 patients low dose heparin, peri- and postoperatively given subcutaneousely (Liquemin subcutan Roche) 2 × 5000 U twice daily for one week, was compared with oral anticoagulants. Deep vein thrombosis, diagnosed clinically and by the 125-J-fibrinogen test, was less frequent in the heparin group (2,3%/4,6%). However, the incidence of pulmonary embolism was rather high (6 cases in the heparin group, only one with oral anticoagulants). Mild postoperative hemorrhage occured more often with heparin, but the incidence of severe hemorrhage remained the same (4,5%).

These results suggest to examine a combination of the two methods: low dose heparin perioperatively, oral anticoagulants in the postoperative course.
Heparin Precipitable Fraction (HPF, “Cryofibrinogen”) from Dermatological Patients
Authors: Fyrand O. , Kierulf P. , Solum N. O.
Published: June 2019

Heparinized plasma from certain dermatological patients mainly with psoriasis arthropathica demonstrated a precipitable fraction (HPF) when left at 4° C for 12 hours. The yield of isolated HPF-protein was 1.5-6.5 mg per ml of plasma, the clottability being of about 50-85 per cent. HPF consisted of three main components, fibrinogen, albumin and an unidentified protein (X-component). SDS polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol demonstrated the fibrinogen subunit chains to be of normal molecular weights. Quantitative N-terminal analysis demonstrated insignificant amounts of N-terminal glycine, indicating at most traces of soluble fibrin in the isolated HPF. Out of 21 patients with HPF 18 showed a negative ethanol gelation test in plasma, and 17 had no detectable FDP in serum.

The X-component was separated from albumin, subsequent to the removal of fibrinogen by heat precipitation (56° C-10 min), as a precipiatating complex with concanavalin A and could be separated from this by a gel filtration on Sephadex G 150 after dissolution of the complex in 0.5 M α-methyl-D-glucoside/0.3 M NaCl.

A possible interpretation is that HPF consists of a complex between essentially normal fibrinogen and the unidentified X-component with albumin as a main contaminant. The nature of the X-component and its quantitation in plasma in normal and pathological conditions are under study.
Hypercoagulability State in Renal Diseases
Authors: Czarniecki W. , Filipowicz Z. , Golębiewski S. , Kardasiewicz W. , Malanowicz W. , Schreyer K. , Zaleski A.
Published: June 2019

The authors carried out investigations on the blood coagulation and fibrinolysis in renal diseases and found many evidencies of a hypercoagulability state : 1 ) studies on the plasma factors showed among others an increased level of factors I, VII and VIII; 2) studies on the fibrinolytic system an inhibition of the fibrinolysis in euglobulins; 3) Thromboelastographic (TEG) studies: widening of the maximum TEG amplitude (increased “Emx” index) and a tendency to shortening of “r” and “k” segment; 4) Determination of the half time of radioactivity decay of fibrinogen (T½ 131J fibrinogen) showed a significant reduction of the T½ J fibrinogen; 5) the paracoagulation test was positive in many cases; 6) Fibrinogen and fibrin degradation products (FDP) were increased in serum and urine of many patients. The results were analysed in different renal diseases and in cases of renal insufficiency separately. The findings speak for an increased tendency for clotting in the renal diseases and are very important for pathogenesis and treatment.
Thrombokinetic Study for Evaluation of Anti-Platelet Agents on Cardio-Vascular Disorders
Authors: Kuramoto A. , Ihara A. , Taketomi Y. , Uchino H. , Taguchi K.
Published: June 2019

To predict and establish the early prophylactic therapy in thrombogenic disorders, we applied 51Cr-labeled platelet survival study (Acta Haemat. Jap. 29, 809, 1966) along with body scanning, to detect early stage of platelet deposition (platelet adhesion) on the injured vascular endothelium and surface of artificial heart valve(s).

In a case of diffuse thromboangitis, markedly decreased survival (T½ = 0.65 days) was noticed with increased platelet turn over (PTO), which reflected increased number of megakaryocyte in the bone marrow. In a case of diffuse skeletal haemangioma, 51Cr-labeled platelets were sequestered in the involoved bone, with short T½ (= 3.4 days) but minimal destruction in reticuloendothelial system. Eight cases under post operative observation after artificial valve replacement with high dose of dipyridamole, showed short survival (T½ = 3.48±0.75), slightly decreased recovery (40.67±16.7%), and two to three times increase of PTO. In two of them, we could forecast thrombotic episodes prior to clinical manifestation based on short survival (T½ = 2.3 and 2.6 days respectively), in spite of marked decrease of glass beads retension. The group under the therapy; e.g. dipyridamole and aspirin, are under investigation.
Fibrin Monomer Polymerization in Liver Disease
Authors: Green G. , Dymock I. W. , Thomson Jean M. , Poller L.
Published: June 2019

Despite a few reports of abnormal fibrin monomer polymerization in liver disease, particularly primary hepatoma, the true incidence of this phenomenon remains to be determined. The unexplained frequency of prolongation of the thrombin-fibrinogen and reptilase times in such patients suggest it is more common than previously suspected.

Over a hundred patients with hepatocellular dysfunction or jaundice have been screened for evidence of abnormal fibrinogen polymerization by a calorimetric method utilizing reptilase. The results have been compared with normal controls and patients with diverse diseases but normal liver function.

Of the patients with primary hepatocellular disease such as cirrhosis and acute liver damage over a quarter exhibited abnormal fibrinogen polymerization. In addition these same patients had prolonged thrombin-fibrinogen and reptilase times, this latter test being the most reliable single index of the presence of abnormal polymerization.

In patients with jaundice due to extra-hepatic biliary obstruction abnormal fibrin monomer polymerization was not observed.

These findings may have important implications in the aetiology of the coagulation defect of liver disease.
Emerging Factors Implicated in Fibrotic Organ–Associated Thrombosis: The Case of Two Organs
Authors: Leiva Orly , Bekendam Roelof H. , Garcia Brenda D. , Thompson Cristal , Cantor Alan , Chitalia Vipul , Ravid Katya
Published: June 2019

Thrombosis is at the heart of cardiovascular complications observed in specific diseases. A heightened thrombosis risk above that in general population in diseases such as myelofibrosis and chronic kidney disease implicates disease-specific mediators of thrombosis. This relative lack of information regarding the mechanisms of thrombosis in specific organ pathologies hitherto has remained limited. Evolving literature implicates some soluble factors in the blood of patients with discrete disorders, inflicting fundamental changes in the components of thrombosis. In this era of precision medicine, integrating these disease-specific factors in a comprehensive thrombotic risk assessment of patients is imperative in guiding therapeutic decisions. A complex network of mechanisms regulates each organ pathology and resultant thrombotic phenotypes. This review surveys different effectors of thrombogenicity associated with two pathologically fibrotic organs used as model systems, the bone marrow and kidney, as well as focuses attention to a common inducer of fibrosis and thrombosis, lysyl oxidase.
Influence of the solvent in the electronic excitation of aromatic alcohols: Excited state IR-UV of propofol(H2O)8
Authors: León Iker , Fernández José A.
Published: June 2019

It is well known that water plays an important role in the reactivity and dynamics in a solution of molecules in electronic excited states. For example, electronic excitation is usually accompanied by a solvent rearrangement that may also influence the redistribution of the excitation energy. However, there is a lack of experimental data on such processes. Here, we explore the structural changes that follow electronic excitation in aggregates of propofol (2,6-diisopropylphenol) with up to eight water molecules, using a combination of mass-resolved excitation spectroscopy and density functional theory calculations. The molecules of water form a polyhedron around the hydroxyl group of propofol, also interacting with the π cloud of the aromatic ring. Electronic excitation produces a strong structural change in the water superstructure, which moves to an interaction with one of the carbon atoms of the aromatic ring, producing its distortion into a prefulvenic structure. Such deformation is not observed in smaller water clusters or in propofol-phenol aggregates highlighting the decisive role played by the solvent.
Sensitivity of X-ray image detectors: Space charge effects
Authors: Mahmood S. A.
Published: June 2019

A model for calculating the sensitivity of direct conversion X-ray image detectors is developed incorporating the space charge effect. The space charge perturbs the applied electric field across the thickness of the photoconductor, and thus the electric field becomes nonuniform. First, Poisson's equation is solved to obtain the electric field distribution. Then, the continuity equations for both holes and electrons are solved considering the perturbed electric field. Finally, the collected charge is determined from the charge carrier distributions and electric field profile using the Shockley–Ramo theorem. The developed X-ray sensitivity model is applied to polycrystalline mercuric iodide based detectors. The electric field collapses for a critical amount of trapped charge if the ratio of trapped electrons to holes is high (∼0.5). The pinch in electric field slows down the drift of free electrons and hence reduces the sensitivity of the detector. The developed model is fitted with the published experimental data, and the fitted values of effective mobility-lifetime products of charge carriers agree well with the published results. It is found that the space charge reduces the sensitivity in the screen-printed sample more significantly than in the vacuum deposited sample.
Pulse contrast enhancement via non-collinear sum-frequency generation with the signal and idler of an optical parametric amplifier
Authors: Cunningham E. , Galtier E. , Dyer G. , Robinson J. , Fry A.
Published: June 2019

We outline an approach for improving the temporal contrast of a high-intensity laser system by >8 orders of magnitude using noncollinear sum-frequency generation with the signal and idler of an optical parametric amplifier. We demonstrate the effectiveness of this technique by cleaning pulses from a millijoule-level chirped-pulse amplification system to provide >1012 intensity contrast relative to all prepulses and amplified spontaneous emission >5 ps prior to the main pulse. The output maintains percent-level energy stability on the time scales of a typical user experiment at our facility, highlighting the method's reliability and operational efficiency. After temporal cleansing, the pulses are stretched in time before seeding two multipass, Ti:sapphire-based amplifiers. After re-compression, the 1 J, 40 fs (25 terawatt) laser pulses maintain a >1010 intensity contrast >30 ps prior to the main pulse. This technique is both energy-scalable and appropriate for preparing seed pulses for a terawatt- or petawatt-level chirped-pulse amplification laser system.
Comparing executive functions in monolinguals and bilinguals
Authors: Whitford Veronica , Luk Gigi
Published: June 2019

Research on bilingualism and executive functions has primarily focused on the presence or absence of an advantage, based on group comparisons between monolinguals and bilinguals. This research rests on two assumptions: first, that participant groups are mutually exclusive, and second, that important statistical practices are upheld. These assumptions, however, are linked to participant-related characteristics and data diagnostic procedures, which are often underreported. Importantly, bilingualism is a dynamic experience, reflecting how individuals interact with their environment through different languages. This interactional experience is essential for grouping participants within studies, and for drawing comparisons across studies. This paper addresses why claims based on between-group investigations of bilingualism and executive functions are insufficient, particularly when research contexts are not considered, and proposes future research directions for the field.
Referring expressions and executive functions in bilingualism
Authors: Sorace Antonella
Published: June 2019

Recent research has shown that the bilingual experience has positive effects on non-linguistic cognition (Bialystok, 2009; Costa & Sebastian-Gallés, 2014) but also negative effects on language, for example on vocabulary size and lexical fluency (Pearson et al., 1993). While most of the linguistic ‘disadvantages’ of bilingualism have been discussed in the lexical domain, this question is scaled up here to the sentence level and a novel theoretical framework is proposed which explicitly connects psychological and linguistic research. It is suggested that the bilingual experience may (a) affect the reciprocal interactions between language and general cognition, and (b) modulate the relation between components of executive functions. These effects may in turn influence the processing of particular linguistic structures, such as anaphoric expressions, and lead to bilingual-monolingual differences that could be regarded as ‘disadvantages’ but are in fact the result of normal adaptive changes due to the bilingual experience. Future experimental research validating this proposal may benefit both linguistic models of anaphora resolution and psychological models of cognitive control in monolinguals and bilinguals.
Effects of dense code-switching on executive control
Authors: Hofweber Julia , Marinis Theodoros , Treffers-Daller Jeanine
Published: June 2019

Bilingualism is reported to re-structure executive control networks, but it remains unknown which aspects of the bilingual experience cause this modulation. This study explores the impact of three code-switching types on executive functions: (1) alternation, (2) insertion, and (3) dense code-switching or congruent lexicalization. Current models hypothesize that different code-switching types challenge different aspects of the executive system because they vary in the extent and scope of language separation. Two groups of German-English bilinguals differing in dense code-switching frequency participated in a flanker task under conditions varying in degree of trial-mixing and resulting demands to conflict monitoring. Bilinguals engaging in more dense code-switching showed inhibitory advantages in the condition requiring most conflict monitoring. Moreover, dense code-switching frequency correlated positively with monitoring skills. This suggests that dense code-switching is a key experience shaping bilinguals’ executive functioning and highlights the importance of controlling for participants’ code-switching habits in bilingualism research.
Putting together bilingualism and executive function
Authors: Valian Virginia
Published: June 2019

Three important issues bear on understanding the connection between bilingualism and executive function. The first is the absence of a fine-grained task analysis for executive functions and other cognitive processes. The second is the absence of a theory of the cognitive mechanisms underlying the deployment of two or more languages and thus the absence of a solid basis on which to make predictions about what domain-general performances, if any, bilinguals should excel in. The third is the relation between neural and behavioral consequences of bilingualism. These three issues must be taken in account in trying to understand the variability among findings showing benefits of bilingualism for executive function.
Interactions among speed of processing, cognitive control, age, and bilingualism
Authors: Marton Klara , Gazman Zhamilya
Published: June 2019

Bilingual children often exhibit superior speed of processing compared to monolingual peers in cognitive control tasks (e.g., Bialystok, 2010). In this chapter, we focus on the interactions among processing speed, cognitive control, age, and bilingualism. Individual differences in speed of processing reflect variation in participants’ skills and in task complexity. The more complex a task, the more cognitive control is involved (Cepeda, Blackwell, & Munakata, 2013). Age also interacts with speed of processing and cognitive control; the same speed of processing task may require more and/or different cognitive control processes at different ages. Furthermore, in bilingual children, speed of processing and cognitive control are associated with different components of their bilingual experience, such as language proficiency and age of acquisition. The cognitive control account (Cohen, 2017) provides a useful framework for studying information processing in bilingual children because it emphasizes the flexibility and adaptation of the cognitive system in response to changing contexts.
Teasing apart factors influencing executive function performance in bilinguals and monolinguals at different ages
Authors: Gathercole Virginia C. Mueller , Thomas Enlli Mon , Viñas Guasch Nestor , Kennedy Ivan , Prys Cynog , Young Nia , Roberts Emily J. , Hughes Emma K. , Jones Leah
Published: June 2019

This study attempts to tease apart a variety of factors that may contribute to performance on executive function tasks. Data from the Simon task are re-examined to determine the contributions of age, SES, language proficiency/vocabulary, general cognitive performance, and bilingualism on performance. The results suggest influence from a variety of factors, with major contributions from relative age and from language proficiency, as measured by vocabulary. Bilingualism showed some effect in relation to older adults’ accuracy of performance, in both congruent and incongruent conditions, but not to reaction time.