bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of Haemophilia in Sweden
Authors: Nilsson Inga Marie 
Published: July 2018

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.
Hemophilia Care in Italy
Authors: Mannucci P. M , Ruggeri Z. M 
Published: July 2018

SummaryTwenty specialized centres for the care of hemophilia and allied disorders have now been established in Italy. Their geographic distribution is uneven and the number is considered inadequate. Financial support is provided by regional Health Departments or by University and General Hospitals; a bill recognizing hemophilia as a social disease entitles the centres to an annual grant from the State or Regional Boards. Less than half of factor VIII employed in the management of hemophilia A is supplied as a cryoprecipitate from hospital blood banks; the rest is imported from commercial manufacturers who also satisfy all the demand for prothrombin complex concentrates. Commercial freeze-dried concentrates can also be obtained free of charge at pharmacies by hemophiliacs covered by national social security schemes. This arrangement facilitates home treatment, which appears the ideal form of management in a country with the geographical features of Italy. In Lombardy, a bill allows hemophiliacs or their relatives to give infusions after adequate instruction. All this has been a great help in achieving more modern management of hemophilia; however, dependence on imported commercial concentrates appears unreasonable on a long-term basis, and major efforts should be directed towards developing a national program for manufacturing blood components.
Management of Hemophilia in France
Authors: Allain Jean-Pierre 
Published: July 2018

SummaryTwo important factors concerning the management of hemophilia in France are considered.The supply of factors VIII and IX for replacement therapy meets the current demand but as the demand increases with the development of self-infusion programs, the production will also have to increase. This can only be done through more effective use of all of the blood components and will require careful evaluation of the needs of each patient.Programs which teach self-infusion and the other aspects of home care are gradually allowing the hemophiliac and his family better understanding of the disease. These programs are developing slowly in France but must be expanded to improve the general care of all French hemophiliacs.
Purification and Properties of Human Factor IXa
Authors: Váradi Katalin , Elödi Susan 
Published: July 2018

SummaryHuman factor IXa was purified 5,000-fold from serum by ion exchange chromatography. The preparation was free from other clotting factors. Both pH sensitivity and heat stability of purified factor IXa appeared to be different from those of factor IX in the plasma. The molecular weight of human factor IXa is 80,000 as estimated from gel-filtration experiments. Modification of seryl or histidyl side chains abolished the activity of factor IXa.
In Vivo Antiaggregatory Action of Platelet-Activating Factor in Beagle Dogs: Role for Prostacyclin
Authors: Hermán Ferenc , Magyar Kálmán , Filep János G 
Published: July 2018

SummaryThe effects of platelet-activating factor (PAF) on in vivo platelet aggregation were studied in anaesthetized beagle dogs by using the extracorporeal filter-loop technique. Intraarterial administration of PAF caused an immediate increase in filter pressure, indicating enhanced in vivo platelet aggregation. Intravenous administration of PAF (3-100 ng kg−1) resulted in a transient dose-dependent inhibition of spontaneous platelet aggregation on the filter with concomitant elevation in plasma 6-keto-PGF1Α levels. These changes were significantly attenuated by pretreatment of the animals either with BN 52021 (4 mg kg−1), a specific PAF receptor antagonist or with acetylsalicylic acid (25 mg kg−1). Intraarterial infusion of exogenous prostacyclin at concentrations similar to those observed following intravenous PAF administration, resulted in a transient inhibition of the spontaneous platelet aggregation. These data provide evidence for prostacyclin release in response to PAF, and suggest that prostacyclin may mediate the in vivo anti-aggregatory action of PAF in anaesthetized dogs.
MCI–9042, a New Antiplatelet Agent Is a Selective S2-Serotonergic Receptor Antagonist
Authors: Hara H , Osakabe M , Kitajima A , Tamao Y , Kikumoto R 
Published: July 2018

SummaryMCI–9042, (±)–1–[2–[2–(3–methoxyphenyl)ethyl]phenoxy]–3–(dimethylamino)–2–propyl hydrogen succinate hydrochloride inhibited platelet aggregation induced by collagen and secondary aggregation by ADP or epinephrine at 10−6 M level in platelets of various species. The antiplatelet effect of MCI–9042 was potentiated in aggregation induced by a combination of serotonin with collagen. IC50 value of human platelet aggregation by the serotonin plus collagen was 1.0 × 10−7 M. MCI–9042 inhibited serotonin release accompanied with collagen-induced platelet aggregation, while it did not affect serotonin uptake into platelet. MCI–9042 also potently inhibited the S2-serotonergic receptor-mediated contraction of rat caudal artery by serotonin in a competitive manner with a Ki value of 1.79 × 10–8 M, while Si receptor- or adrenergic receptor-mediated vasoconstriction was inhibited more weakly. Platelet adhesiveness, c-AMP level in platelets and the conversion of arachidonic acid to thromboxane A2 were not influenced by MCI–9042. These results suggest that MCI–9042 is a selective S2-serotonergic receptor antagonist, exhibiting the inhibition of S2-serotonergic potentiated platelet aggregation and the suppression of blood vessel constriction mediated by S2-serotonergic receptor.
Prevention of Deep Vein Thrombosis following Total Hip Replacement by Low Molecular Weight Heparinoid
Authors: Hoek J A , Nurmohamed M T , Hamelynck K J , Marti R K , Knipscheer H C , ten Cate H , Büller H R , Magnani H N , ten Cate J W 
Published: July 2018

SummaryWe assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s. c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively.The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P <0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P <0.005) and isolated calf-vein thrombosis (31% to 7%; P <0001.No major hemorrhage was observed. The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P <0.05).During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group.We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required.
Liver Blood Flow as a Major Determinant of the Clearance of Recombinant Human Tissue-Type Plasminogen Activator
Authors: de Boer A , Kluft C , Kroon J M , Kasper F J , Schoemaker H C , Pruis J , Breimer D D , Soons P A , Emeis Jef J , Cohen Adam F 
Published: July 2018

SummaryThe influence of changes in liver blood flow on the clearance of rt-PA was studied both in healthy subjects and in a perfused rat liver model. Liver blood flow in healthy subjects was documented indirectly by the clearance of indocyanine green (ICG). Exercise reduced liver blood flow on average by 57% with a 95% confidence interval (95% Cl) ranging from 51% to 62% (n = 5) and increased plasma levels of rt-PA activity (after an i. v. infusion of 18 mg of rt-PA over 120 min) by 119% (95% Cl, 58% - 203%) and rt-PA antigen by 91% (95% Cl, 30% - 140%). In the perfused rat liver model it was shown that halving or doubling of the physiological flow rate of a perfusate, containing rt-PA caused a proportional change in the clearance of rt-PA, while the extraction of rt-PA by the liver remained similar. In conclusion, liver blood flow is a major determinant of the clearance of rt-PA. This may have important implications for dosage of rt-PA in patients with myocardial infarction.
Aprotinin Does Not Inhibit the Release of PGI2 or vWF from Cultured Human Endothelial Cells
Authors: Royston B D , Royston D , Coade S B , Morgan D M L , Pearson J D 
Published: July 2018

SummaryThe release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin had any effects on these endothelial cell reactions. These end-points were chosen to indicate if this serine protease inhibitor caused alterations in the control of haemostatic function by endothelium, in the light of the improvement in haemostasis seen in patients given aprotinin therapy at the time of open heart surgery. Stimuli used to promote secretion of prostacyclin and vWF were human α-thrombin, histamine, protamine sulphate, poly-L-lysine and phor-bol myristate acetate. Aprotinin (30 pM) had no significant effect on the basal or stimulated release of PGI2 or vWF from HUVEC.
A Decrease in Plasminogen Activator Inhibitor-1 Activity after Successful Percutaneous Transluminal Coronary Angioplasty Is Associated with a Significantly Reduced Risk for Coronary Restenosis
Authors: Huber Kurt , Jörg Maria , Probst Peter , Schuster Ernst , Lang Irene , Kaindl Fritz , Binder Bernd R 
Published: July 2018

SummaryTo determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTC A), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p <0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p <0.05 to p <0.0005).
Study of Aggregate Formation in Region of Separated Blood Flow
Authors: Morton William A , Parmentier E. Marc , Petschek Harry E 
Published: July 2018

SummaryThe formation of platelet aggregates which embolize to the peripheral circulation has previously been noted as a significant deleterious effect resulting from both intra-and extracorporeal artificial circulatory devices. Utilizing the stagnation point flow experiment, which permits visualization during flow of aggregate formation on first contact of blood with an artificial surface, the formation of freely floating aggregates has been observed in separated flow regions. Embolization from the separated flow has also been noted. Comparison of observed growth rates with a hydrodynamic model suggests that sufficient activation has occurred within the separated region so that platelets stick on virtually every collision. Some criteria are also suggested which correlate with the flow conditions affecting aggregate formation. At high flow rates, where freely floating aggregates do not form, significant surface thrombi are found.
Blood Changes in Atherosclerosis and Long After Myocardial Infarction and Venous Thrombosis
Authors: O’Brien John R , Etherington Michael D , Jamieson Sandra , Lawford Piers , Lincoln S. V , Alkjaersig Norma J 
Published: July 2018

SummaryThe following clinical groups of volunteers were studied: patients long after recovery from myocardial infarction (MI), others after recovery from deep vein thrombosis (DVT), patients with intermittent claudication, with diabetes, and male and female controls who were well matched. All were subjected to many platelet and clotting tests together with clinical, biochemical and haematological measurements in an attempt to find long term abnormalities in these various diseases.The male Mis differed very significantly from the controls in having much more heparin neutralizing activity (P < 0.001) and less anti-thrombin (P < 0.01). Less significantly, some bleeding time tests indicated less bleeding and the patients’ platelets were larger. The females with MI had in general the same abnormalities but to a lesser degree. The patients with intermittent claudication, none of whom had a history of MI, had almost the same abnormalities and to the same degree. In deep vein thrombosis the heparin neutralizing activity was also clearly increased; the other tests were generally in the same direction but many were not significant. The diabetics had shorter bleeding times but little else abnormal relative to the controls, suggesting a different pathological process.When all male patients and controls were “scored” according to the degree of atherosclerosis there was a close overall correlation between the degree of atherosclerosis and the increase in the HNA level (r = — 0.50, n = 66, P < 0.001) and the decreased anti-thrombin (r = — 0.25, n = 66, P < 0.05).The platelet abnormalities might indicate activated platelets with increased turnover; decreased anti-thrombin not only favours clotting but could suggest that clotting has occurred. Thus it is suggested that all the abnormalities may be accounted for if minor intravascular or mural coagulation occurs more or less permanently in these patients. This activation of the haemostatic mechanism towards coagulation could be related to the cause of atherosclerosis, or it could be the result. The mechanisms predisposing to or following DVT are somewhat different ; some may be shared. The nine diabetics are clearly quite different.The reported abnormalities found consistently in two studies may (1) illuminate pathogenesis; (2) indicate groups or even individuals at risk. (3) Improvement of the tests by appropriate therapy might justify a clinical trial of that therapy. (4) The high HNA in these syndromes may be relevant to any contemplated heparin therapy.
Effect of Anabolic Steroids on Plasma Antithrombin III
Authors: Walker I. D , Davidson J. F , Young P , Conkie J. A 
Published: July 2018

SummaryThe effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three α-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-α-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma α2-macroglobulin. The effect on plasma α1antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-α-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.
Local Fibrinolysis as a Mechanism for Haemorrhage
Authors: Nilsson Inga Marie 
Published: July 2018

SummaryMost human tissues and body fluids contain activators of plasminogen. The highest concentrations occur in the uterus, adrenals, lymph nodes, prostate, thyroid and meninges. The tissue fibrinolytic activity is related to the presence of vascularized connective tissue. The urine has a high fibrinolytic activity owing to its content of urokinase. The fibrinolytic activity in the tissues does not cause haemorrhage in intact tissues. However, any injury of such tissues can result in the release of activators and thereby maintain and prolong various forms of bleeding. Local fibrinolysis may thus be a contributory cause of bleedings from many organs.There is evidence that local fibrinolysis can maintain and aggravate bleeding from the uterus (certain cases of menorrhagia, after conisation, after insertion of intrauterine devices), the urinary pathways (prostatectomy, various operations on the bladder), the digestive tract (ulcerative colitis, erosive haemorrhagic gastroduodenites), oral cavity (tooth extractions) and the nasal mucosa. It has also been found that subarachnoid haemorrhage is followed by increased local fibrinolysis in the cerebrospinal fluid.It has been shown that a variety of drugs such as EACA, AMCA and PAMBA can inhibit both normal and, in certain situations, increased fibrinolytic activity in tissues and body fluids and thereby stop or suppress bleeding.
Culture of Arterial Endothelial Cells
Authors: Booyse Francois M , Sedlak Bonnie J , Rafelson Max E 
Published: July 2018

SummaryArterial endothelial cells were obtained from bovine aortae by mild treatment with collagenase and medium perfusion. These cells were cultured in RPMI-1640 medium containing 15 mM Hepes buffer and 35% fetal calf serum at pH 7.35. Essentially ah (90–95%) the effluent cells were viable and 80% of these cells attached to the substratum within 1 hour. Small patches of attached cells coalesced to form confluent monolayers in 3–5 days. Confluent monolayers of endothelial cells consisted of a homogeneous population of tightly packed, polygonal cells. Selected cultures were serially subcultured (trypsin-EDTA) for 12–14 months (30–35 passages) without any apparent change in morphology or loss of growth characteristics. Primary and three-month old (15 passages) cultures had population doubling times of 32–34 hours and 29–31 hours, respectively. These cells (primary and subcultures) did not require a minimum cell number to become established in culture. Bovine endothelial cells (primary, first, fifth and thirteenth passages) were characterized ultrastructurally by the presence of Weibel-Palade bodies, pinocytotic vesicles and microfilaments and immunologically by the presence of thrombosthenin-like contractile proteins and Factor VIII antigen. The intercellular junctions of post-confluent cultures stained specifically with silver nitrate. From these data, we concluded that identifiable endothelial cells could be obtained from bovine aortae and cultured and maintained for prolonged periods of time.