bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malaric Thrombopathy
Authors: Ospina L , Bernal M D E , Santos C 
Published: May 2019

The purpose of this investigation was to demonstrate platelet aggregation defects in patients infested with Plasmodium, giant and normal platelets counts.Laboratory studies were performed by using a “Payton Aggregometer”. ADP, Collagen, Epinephrine and Ristocetin as commercial reagents. Coagulation tests were done by regular methods. Thirty out of 31 patients were found to have marked defects in secondary aggregation wave with ADP. Aggregation with Collagen was constantly abnormal. Fifteen patients showed primary and secondary aggregation abnormality with ADP, Adrenaline and Collagen. Aggregation with Ristocetin was always normal. Aggregation defects were not drug induced since the patients were taking no medicines at least five days prior to studies.Studies done in volunteers taking antimalarics, Dipirone, Acetaminophen showed no interference with aggregation. Aggregation abnormalities were mostly found in patients infested with chronic Falciparum malaria.
Most of the patients did not have bleeding manifestations but had multiple organ involvement. We think this platelet defect is a manifestation of some defense mechanism to prevent massive thrombosis frequently found in Falciparum Malaria.
HAEMODIALYSIS INDUCED HYPOXIA: A COMPARISON OF THE EFFECT OF PROSTACYCLIN, METHYL PREDNISOLONE, ULTRAFILTRATION AND BICARBONATE DIALYSATE
Authors: Dodd N J , Turney J H , Weston M J 
Published: May 2019

In order to test certain hypotheses regarding the cause of arterial hypoxia during haemodialysis(HD),we investigated the effect of:- 1 Heparin bolus-infusion; or heparin plus:- 2.Prostacyclin ( PGI2 ) infusion ( 5ng/Kg/mi n );3. Methyl Prednisolone bolus(30mg/Kg) 30 minutes prior to dialysis; 4. Ultrafiltration for one hour followed by dialysis(UF/HD); 5.40mmo1/l Bicarbonate dialysate instead of standard acetate dialysate . Seven patients on long term HD were examined by all methods. Arterial blood samples were taken before,and at intervals during ,dialysis for blood gases, platelet count,and neutrophil count. All results are expressed as percentage of pre-dialys is value (means).Results fo r each group were tested fo r significance against the Heparin group(l.)using a paired t tes t . The only significant sparing of hypoxia occurred at 60 minutes during UF/HD.PGI2 spared platelets , as we have previously shown. Methyl Prednisolone failed to prevent dialysis induced neutropenia. The mechanism of haemodialysis induced hypoxia remains obscure
Clot Promoting Effect of Platelet-Vessel Wall Interaction
Authors: Hornstra G 
Published: May 2019

When a piece of vascular tissue (rat, rabbit) is incubated in plasma, clotting occurs.
The presence of platelets accellerates this clotting process.Inhibition of vascular prostacyclin (PGI2) production, either by drugs or by inducing arachidonic acid deficiency, causes the platelets to become activated by the vessel wall, resulting in platelet shape change and -aggregation and in a further enhancement of the coagulation response. Hirudin very actively inhibits both aggregation and clotting whereas ADP scavenging has only a weak effect. This indicates that the aggregation response, occurring upon platelet-vessel wall interaction is for the greater part mediated by thrombin.Saturated fat feeding increases the clot promoting effect of the platelet-vessel wall interaction. This appeared not to be due to differences in the production of vascular PGI2or platelet endoperoxides and thromboxanes (measured as malondialdehyde).These findings indicate that:
1. Thrombin, locally generated upon the interaction between damaged vessel wall and blood constituents, contribute to arterial thrombus formation;2. Prostacyclin regulates local thrombin formation via its inhibiting effect on platelet activation;3. The existence of another, platelet bound affector is postulated.
Histochemical And Ultrastructural Study Of The Platelet-Arterial Subendothelium Interaction
Authors: Legrand Y , Bariety J , Birembaut P , Michel H , Fauvel F , Caen J 
Published: May 2019

In order to characterize the subendothelial macromolecules able to interact with platelets rabbit aortas were de-endothelialized and incubated either with chymotrypsin (24 h at 37° C), with a highly purified bacterial collagenase (2 h at 37° C), or with chymotrypsin
followed by collagenase or the reverse. Histochemical ultrastructural studies were performed before and after blood perfusion, using three different staining procedures : tannic acid (for the microfibrillar structures and elastin), ruthenium red (for the polyanions) and two peroxidase-labelled lectins (concanavalin A and ricinus communis (for the detection of saccharidic determinants)). After chymotrypsin, the tannic acid +ve, ruthenium red +ve and lectin +ve microfibrils had been digested ; platelet adherence to the remaining sparse collagen fibrils persisted. After collagenase, these microfibrils are preserved, collagen has been digested, but the platelets can still adhere. After combined incubation with both enzymes, elastin is the only remaining constituent and no platelet adhesion can be observed.These results show that in the rabbit aorta subendothelium besides collagen, microfibrillar glycoproteins are able to interact with human platelets.
In Vitro Synthesis of Bovine Prothrombin in a Purified System
Authors: de Metz M , Vermeer C , Soute B , Hemker H 
Published: May 2019

Coumarin treatment of the cow results in the appearance of a prothrombin precursor (de-carboxyprothrombin) in the blood. We have isolated from bovine liver the enzyme (prothrombin synthase) that is able to convert purified decarboxyprothrombin into prothrombin. Prothrombin synthase is localized in the microsomal fraction and extracted therefrom with a buffer containing 2% Triton X-l00. Further purification of the enzyme was accomplished by column chromatography on Sepharose 4B, DEAE Sephacell and Sephadex G 100. The molecular weight of prothrombin synthase was found to be about 60,000 D. The enzyme activity is defined as the ability to increase the prothrombin concentration at standard conditions and it is measured as a decrease of the clotting time in the one-stage coagulation assay. In the presence of NaH14CO3, radioactive label is incorporated into decarboxyprothrombin, parallel to the generation of prothrombin.After extraction with a suitable organic solvent prothrombin synthase was separated from endogenously bound vitamin K. After extraction the water phase contained the enzyme, the activity of which was completely restored by supplementing the reaction mixtures with vitamin KH2. The organic phase contained the vitamin K as was deduced from U.V.spectra. Prothrombin synthase is dependent on Mn2+and molecular oxygen and is inhibited by warfarin, Cl-K and Cu2+.
Clinical Trials in the Secondary Prevention of Myocardial Infarction and Stroke
Authors: Armitage P 
Published: May 2019

In the 30 years or so since adequate clinical trials were first conducted the basic principles have scarcely changed. Randomization remains an essential ingredient. Trials have increased in size and duration, and standards of design and execution are now high. Particular attention should be paid to the effect of baseline variables, for correcting imbalance and improving precision, and also to reveal interactions between these variables and the treatments.Trials in the secondary prevention of stroke and myocardial infarction, as in other fields, frequently appear to engender controversy. This is partly due to dissenting views about aspects of the protocol on which choices had to be made (perhaps an argument for flexibility in the protocol); and partly due to termination at an inconclusive stage. The ethical dilemma prevents any easy solution, but it is suggested that early stopping should only be allowed when evidence for a difference is very strong.Different approaches to the handling of protocol departures are discussed; the pragmatic approach, with inclusion of all cases after randomization, is advocated.Factorial designs are likely to be increasingly adopted, in view of the pressure of new drugs and the need to economise in the large numbers of patients required. Some interpretative problems are discussed.
Decreased Reactivity of Plasmin-Streptokinase Towards α-2-Antiplasmin
Authors: Cederholm-Williams S , Lijnen H , De Cock F , Collen D 
Published: May 2019

Plasmin (P) is very rapidly (rate constant 2 x 107M-1s-1) inactivated by α-2-antiplasmin (A), and blocking of the lysine binding sites (LSB) of plasmin reduses this rate 50 fold (Eur.J.Biochem.84, 573-578, 1978). Using purified reactants and the plasmin substrate D-Val-Leu-Lys-pNA (S 2251) the influence of streptokinase (SK) on the reaction between P and A was examined. Addition of SK to P reduces the reaction rate with A in a sigmoidal fashion. Assuming the formation of a reversible bimolecular P:SK complex which is unreactive towards A then the dissociation constant Kd of this complex is less than 10-9M. The LSB of P does not play a role in this interaction since similar Kd values are found with modified P, lacking LSB and in the presence of 0.3 mM 6-aminohexanoic acid which blocks the LSB. The P:SK complex is only very slowly inhibited by A with a rate constant < 5 x 102M-1s-1.It is concluded that the α-2-antiplasmin is less reactive towards the plasmin streptokinase complex due to a modification of the active center of plasmin rather than an effect upon the binding sites.
Determination of α1-Antitrypsin with A Chromogenic Peptide Substrate Methodology and Clinical Application
Authors: Witt I. , Lill H. , Karitzky D. , Flad H. 
Published: May 2019

α-Antitrypsin (α-AT) is a relatively unspecific inhibitor of proteinases. The co-dominant hereditary defect of the protein can be associated with obstructive pulmonary emphysema in adulthood or with juvenile hepatocirrhosis.A rapid and reliable method for the determination of α1-AT activity with the chromogenic substrate Z-Val-Gly-Arg-pNA has been developed: a standardized trypsin solution of known activity is allowed to react with the plasma or serum sample and the residual trypsin activity determined after incubation. The difference between the initial and residual trypsin activities corresponds to the α1-AT activity. The assay is carried out in tris/HCl-buffer at pH 8.0 (ionic strength=0.15) and 25°C; measurements are taken at 405 nm. Both kinetic and 2-point measurement is possible. The coefficient of variation for day-to-day precision is <5%.The following guide values were determined on 15 healthy probands: 141 ± 15 inhibitor U/ml for plasma, and 130 ± 25 inhibitor U/ml for serum.The minute volume of plasma or serum used precludes non-specific reactions of the substrate with other proteases. Homozygous carriers of this protein defect can be accurately identified by means of this test.
Congenital Antithrombin III Deficiency in 3 Families (7 Affected Members)
Authors: Conard J. , Samama M. , Horellou M. H. , Cazenave B. , Griguer P. , Barsotti J. , Herreman G. , Godeau P. 
Published: May 2019

A congenital Antithrombin III (AT III) deficiency affecting 7 members of 3 families is reported.The first throrabo-embolic accidents were observed between the age of 22 and 35 : they were spontaneous or occured after delivery or oral contraception. in one patient, a deep vein thrombosis was observed during heparin treatment. in 2 cases, recurrent pulmonary embolic episodes required vena cava ligation. No thromboembolic accident was observed during oral anticoagulation.AT III was measured by an amidolytic method and by the Mancini method on plasma and serum ; the antithrombin activity was determined on serum by the von Kaulla method. in 7 patients, a decreased AT III was found by all the methods performed. The AT III level was around 50 % in patients treated or not by oral anticoagulants One patient was studied during heparin treatment and then under oral anticoagulants : AT III levels were lower under heparin.
Microheterogeneity of Human Factor VIII
Authors: Mourik J.A. van , Hellings J. A. , Hoorweg E. M. 
Published: May 2019

Human factor VIII is a glycoprotein and tends to form a variety of large aggregates, the presence of which was demonstrated by a number of techniques including the use of large pore gel chromatography and electrophoresis using a polyacrylamide gel system designed for high molecular weight aggregates. Factor VIII aggregates can be fractionated in part according to molecular size. Reduction of these polymers by 2-mercaptoethanol results in presumably identical fragments suggesting that all polymers, though differing in size, are composed of identical subunits.Factor VIII aggregates are particularly sensitive to proteolytic breakdown by trypsin and plasmin as judged by large pore polyacrylamide gel electrophoresis. Short-term incubation of factor VIII with trace quantities (equivalent to plasmin- or trypsin-like activities present in normal plasma) of these enzymes respectively results in substantial fragmentation with concurrent loss of both factor VIII procoagulant and von Willebrand factor activity. However, factor VIII activity is lost prior to discernible protein fragmentation whereas von Willebrand factor inactivation is associated with advanced protein degradation. When the ionic strength of the medium is lowered the susceptibility of factor VIII to proteolytic breakdown by trypsin is increased dramatically. Interestingly, degradation of factor VIII by plasmin is not affected by the ionic strength. These data, then, provide conclusive evidence of microheterogeneity of normal human factor VIII and may account for the observed heterogeneity of factor VIII on crossed immunoelectrophoresis.
Complement Dependent and Independent Effects of Bacterial Products on Rabbit and Human Platelets
Authors: Semeraro N. , Vermylen J. 
Published: May 2019

The effect of 13 lipopolysaccharides (LPS) from aerobic and two LPS from anaerobic bacteria, two mucopeptides and two meningococcal polysaccharides, on rabbit platelets in citrated and heparinized plasma was studied by aggregometry. The LPS from aerobic bacteria showed variable aggregating activity. LPS from S. Minnesota Re 595 (essentially lipid A) was one of the most active. The two mucopeptides were very active whereas the LPS from anaerobic bacteria and the meningococcal polysaccharides were inactive. These effects were abolished by inactivation of complement and by ethyleneglycoltetraacetic acid (EGTA) indicating that they are dependent on activation of the classical pathway. None of these effects was observed using human platelets.When washed rabbit platelets are mixed with complement-depleted rabbit serum and calcium chloride, generation of thrombin occurs. All the LPS preparations but not the mucopeptides or meningococcal polysaccharides enhanced the rate of thrombin formation to a variable extent. Identical effects have also been found using human platelets (Brit. J . Haemat. in press).It is concluded that LPS affect rabbit platelets by separate complement dependent and independent mechanisms. However with human platelets only the complement independent phenomenon (enhancement of thrombin generation) is observed.
Prostaglandin-Endoperoxides and Cyclic 3′-5′-AMP in Platelets of Patients with Uremia
Authors: Matthias F. R. , Palinski W. 
Published: May 2019

In platelets of normal donors and of patients with chronic renal failure the following determinations were performed: 1. prostaglandin-endoperoxide-formation after N-ethylmaleimide stimulation measured as malondialdehyde; 2. the c-AMP level according to the Gilman-method; 3. the adenylate-cyclase activity in response to prostaglandin E1; 4. aggregation in response to collagen.In comparison to’normal donores the prostaglandin-endoperoxide production was reduced in uremic patients. Plasma of uremics depresses the endoperoxide formation of normal platelets. The basal c-AMP level of platelets of’ patients with renal failure was not significantly changed, whereas the plasma c-AMP level was increased; the activation of the platelets adenylate-cyclase was impaired. The adenylate-cyclase activity of platelets from normal donors was reduced by uremic plasma.. The results are of interest as to the explanation of the bleeding tendency of uremic patients.
The Factor VIII Molecule in Acquired Von Willebrand’s Disease
Authors: Preston F. E. , Malia R. G. , Sampson B. 
Published: May 2019

Four patients with acquired von Willebrand’s disease have been studied. The diagnosis in each case was based on acquired bleeding disorder, negative family history, prolonged bleeding time, low procoagulant factor VIII (F. VIIIC) and factor VIII related antigen (F. VIIIR. A.) activity and impaired ristocetin-induced platelet aggregation responses.Gel filtration studies were performed on plasma samples from each of the four patients and the fractions tested for F. VIIIC activity using a modified kaolin cephalin clotting time. Samples from each patient showed two peaks of procoagulant activity compared with one peak obtained on samples from controls, haemophiliacs and classical von Willebrand’s syndrome.When incubation mixtures of acquired von Willebrand plasma and a source of normal factor VIII are examined by similar gel filtration techniques, it can be shown that the normal F. VIIIC becomes dissociated into sub-units of varying size.Similar results have been obtained by incubating mixtures of the patients’ IgG obtained by ion exchange chromatography and normal sources of factor VIII.It is concluded that acquired von Willebrand’s disease is probably due to an antibody directed against the factor VIII molecule.
An International Collaborative Study of Factor VIII
Authors: Barrowcliffe T. W. , Kirkwood T. B. L. 
Published: May 2019

A collaborative assay was organised to assess the suitability of a replacement for the first International Standard for Factor VIII. Coded samples of a freeze-dried concentrate (proposed 2nd I. S.), the 1st I.S., and a freeze-dried plasma were assayed by 15 laboratories against fresh normal plasma and local standards. Ten laboratories performed 1-stage assays and five 2-stage.The proposed 2nd I. S. had a mean potency of 1.14 International Units per ampoule by direct assay against the 1st I. S.., with no significant difference between one- and two-stage assays. When assayed against a large number of individual normal plasmas, the proposed standard was equivalent to 1.05 ml “average normal plasma” per ampoule. In assays of the common freeze-dried plasma against the 1st I. S., there was a significant difference between assay methods, the 1-stage assays giving higher results for the plasma than the 2-stage. This difference between assay methods confirms results from other collaborative studies, and it seems likely that the 2-stage method is detecting relatively more activity in the concentrate standards.It was agreed by the participants that the proposed material is suitable, in terms of stability and comparability with other materials, to serve as the 2nd International Standard for Factor VIII. The standard was established by WHO at the 28th meeting of the Expert Committee on Biological Standards, with a potency of 1.1 IU per ampoule.
Antistreptokinase Titres Before, During and after Streptokinase Therapy
Authors: Naidu R. , Kὂstering H. , Guerrero M. A. , Hampe R. 
Published: May 2019

We usually prefer streptokinase therapy for thrombolytic treatment in patients with thromboembolism. For this therapy it is necessary to know the antistreptokinase (ASTK) titre, in order to calculate the initial dose, due to streptokinase resistance in some patients. The ASTK titres in 108 normal subjects and in 442 patients were examined and showed that 4.66% needed one million units streptokinase, 7.86% 500,000, 21.7% 250,000, 23.3% 100,000 and 42.5% 50,000 units. The results varied greatly in the different groups of patients.It is sometimes necessary to repeat streptokinase administration to patients. The ASTK titre was therefore determined daily for three weeks in 25 patients before, during and after streptokinase therapy. In another group of 70 patients, who had previously received this treatment for up to 72 months, the ASTK titres were elevated and 7 days following the beginning of the new treatment had increased to 15 million units and between the 11th and 16th day to 30 million units. This was followed by a slow but steady decrease to 6 million after one month, 2.5 million after 2 months and 900,000 after 3 months. After six months were were most often normal values and low titres were rarely seen. This means that thrombolytic therapy could be repeated at this time.
Low Molecular Weight Factor VIII: A Comparison of the Electrophoretic Maps of the Normal and Hemophiliac Molecule
Authors: Rock G. A. , Cruickshank W. H. 
Published: May 2019

Considerable debate exists as to the relative structure of normal and hemophiliac Factor VIII. In order to obtain some insight into the differences which exist at the molecular level we examined the various subunits found after dissociation of Factor VIII from these two populations.Factor VIII was obtained by column chromatography of either cryoprecipitate or concentrated plasma on Sepharose CL6B. The protein eluting at the void volume was rechromatographed in buffer containing 0.25 M CaCl2. Under these conditions, both normal and hemophiliac Factor VIII underwent dissociation with an identical elution pattern. The low molecular weight faction from normal Factor VIII displayed procoagulant activity: that from the hemophiliac did not.As determined by their elution volume and ultrafiltration, the molecular weights were identical. When digested with pepsin (protein: pepsin 50:1) for 16 hours at 37°C and “mapped” by pH 6.5/2.1 paper electrophoresis the two compounds were significantly different in the neutral and acidic peptide regions and identical in the basic region.It therefore appears that the inactivity of hemophiliac Factor VIII is a consequence of an amino acid substitution or deletion in the low molecular weight portion of the molecule rather than a complete absence of the procoagulant molecule.
Platelet Suppression Therapy in Arterial Disease: Present Status
Authors: Blakely J. A. 
Published: May 2019

Arterial disease is a severe test of clinical trials methodology. Results to date have defined areas for further study, but clinical indications are not established. Dipyridamole reduces emboli from prosthetic heart valves but applicability to less thrombogenic valves is uncertain. Transient cerebral ischemic attacks are physiologically appropriate and there is preliminary evidence of reduced attacks with Sulfinpyrazone, none with Dipyridamole, and favorable case reports with Aspirin. Effects on stroke and death in patients presenting with TIA or stroke are under study. Sulfinpyrazone has failed to prolong patency time after peripheral vascular surgery. Administration of aspirin and of Sulfinpyrazone to elderly populations has shown no detectable benefit from Aspirin, and has suggested that Sulfinpyrazone should be further studied in patients recovered from thrombotic stroke. The greatest potential benefit may be secondary prevention of myocardial infarct, but to date efficacy has neither been demonstrated nor excluded. Studies in progress include: ASA and/or Sulfinpyrazone and TIA, stroke and death in patients with TIA; ASA with and without Dipyridamole in patients with TIA: Sulfinpyrazone and survival after recovery from thrombotic stroke; Secondary prevention of myocardial infarct with ASA, ASA or ASA + Dipyridamole, Sulfinpyrazone, and Clofibrate; Sulfinpyrazone, ASA, and ASA with anticoagulants and emboli from prosthetic valves. Platelet survival studies may permit selection of populations likely to benefit and assessment of adequacy of therapy.Hypotheses tested by clinical trial must be distinguished from hypotheses formulated from retrospective analysis, and methods must permit effects of treatment to be distinguished from differences in risk.