bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORG 10172 CAUSES INCREASED URINARY BLEEDING AFTER TRANSURETHRAL PROSTATECTOMY (TURP)
Authors: Gallus A , Murphy W , Nacey J , Magnani H 
Published: August 2018

Standard anticoagulant prophylaxis is rarely used after TURP because it is believed to increase urinary bleeding. Org 10172 prevents experimental thrombosis and causes less bleeding than heparin in animals. We therefore evaluated its influence on urinary blood loss after TURP in a double blind, placebo controlled, study, which examined the effects of three Org 10172 regimens (750 antiXa u/day, 500 u bid, 750 u bid), given subcutaneously. Pilot studies have shown that 750 u bid prevents venous thrombosis (VT) after thoracotomy. At each dose level, 10 patients received Org 10172 and 6 placebo. Because patients had spinal anesthesia, they received their first injection of trial drug after anesthesia was established and immediately before surgery. Bleeding was estimated by measuring urine hemoglobin (Hb) and volume. The three dosage groups all showed trends towards increased postoperative urine bleeding in Org 10172 treated patients, but no apparent increase in blood loss with increasing dose, so they were pooled for analysis:Hence, Org 10172 in doses which are likely to be needed for VT prevention causes a moderate increase in urine bleeding after TURP.
THE THROMBOTIC COMPLICATIONS OF TWO GROUPS OF PATIENTS WITH DIFFERENT INR THERAPEUTIC RANGES. THE NECESSITY OF INTENSE ORAL ANTICOAGULANT TREATMENT
Authors: Kontopoulou-Griva Ir , Spiliotopoulou J , Digenopoulou L , Georgopoulos J 
Published: August 2018

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally acceptable standarised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over and under coagulation and uncertainty in the therapeutic range. The International Normalised Ratio (INR) can safely be applied in patients on oral anticoagulants.We present two Groups of patients under long term anti coagulation, mainly because of prosthetic heart valves that have recently been added to our outpatients clinic. These patients were till then attended by two cardiologists with different attitudes on the intensity of the anticoagulant treatment. The thromboplastin reagent used is that of ox origin and the results are expressed on INR.The Group A with 32 patients had at the time that we started attending them an INR x = 1,80 ± 0,48 and a daily dose of acenocoumarol x = 1,65 ± 0,51.The Group B with 49 patients had an INR x = 2,75 ± 0,51 and a daily dose of acenocoumarol x = 2,52 ± 1,53.Seven patients of the Group A referred thrombotic complications, while three patients of the Group B referred transiant thrombotic complications.The statistical analysis with the t-test of the INR between the two Groups is p<0,001 while that of the thrombotic complication with the x2 is p<0,05.The introduction of the INR and the acceptance by the medical people of the necessity of the intense oral anticoagulant treatment especially on high risk patients with mechanical heart valves as is the majority of the presented patients, will minimize the thromboembolic complications without high risk of bleeding.
PROTEIN C RESPONSE TO INDUCTION AND WITHDRAWAL OF ORAL ANTICOAGULANT TREATMENT
Authors: Schofield K P , Thomson J M , Poller L 
Published: August 2018

Protein C (PC) activity and antigen levels have been related to clotting activities of factors VII and X during the induction and withdrawal periods of oral anticoagulant treatment. Both factor VII and PC activities fell rapidly during a gradual induction regime of nicoumalone in six consecutive patients but factor VII showed a more rapid and much more marked depression than PC. In contrast reductions in factor X were much slower. PC antigen although depressed rapidly at the initiation of treatment did not subsequently fall to the same degree as PC activity, The ratio of activity to antigen became progressively smaller.In six further serial patients discontinued from long-term treatment with nicoumalone (mean duration 12-6 months) there was a reversal of the pattern, but with two important differences. Firstly, there was evidence of an excessive rise (“rebound”) of factor VII compared with the steady state levels in these patients; and secondly there was an unexpectedly slow return of PC activity and antigen to normal levels after the oral anticoagulant was withdrawn (levels were still below normal on day 4). Factor X also showed a slow rate of increase, similar to PC activity recovery. These observations lend support to gradual withdrawal of oral anticoagulants after a period of long-term administration. The results suggest that after discontinuation of long-term oral anticoagulants patients may have increased coagulability up to four days.
NORMOTEST. A SIMPLE METHOD FOR DETERMINATION OF FACTOR VII-PHOSPHOLIPID COMPLEX.
Authors: Dalaker K , Janson T L , Prydz H 
Published: August 2018

We have previously described a factor Vll-phospholipid complex (the phospholipase C(PLC)-sensitive component of factor VII) in plasma from pregnant women (1,2) as well as in some men at high risk for cardiovascular disease (3), and in male survivors of acute myocardial infarction (4).Factor VII present in such complexes is markedly activated, and this activation is reversible upon treatment with PLC, which hydrolyses phospholipids to diglycerides.We report here that a highly significant positive correlation was found when the PLC-sensitive component of factor VII was tested in a spesific factor VII test system and in Normotest (Nycomed A/S, Oslo, Norway) (p<0,0001). The Normotest system, which is sensitive for coagulation activities within the normal range, was not influenced by PLC when the enzyme was added immediately before the coagulation reaction was started.We conclude therefor that Normotest is well suited for determination of the factor Vll-phospholipid complex in plasma.References.K. & Prydz, H. Br J Haematol 56, 233-241, 1984Dalaker, 1984. Dalaker, Dalaker, Dalaker,K. Br J Obstet Gynecol 93, 17-21, 1986.K. et al. Br J Haematol 61, 315-322, 1985. K. et al. Submitted.
MONOCYTE STIMULATION IN BLOOD EXPRESSED BY INDUCED THROMBOPLASTIN SYNTHESIS IS CONTROLLED BY THE RELEASE OF ARACHIDONIC ACID AND THE FUNCTION OF PLATELETS.
Authors: Osteurd B , Olsen J O , Wilsgard L 
Published: August 2018

Inhibitors of phoapholipaae A2, block the release of arachidonic acid (20:4) in the cell membrane. Adding such an inhibitor, dibromoacetophenone (20µM) to hepar-inized blood incubated with LPS for 2 hours, blocked totally the induction of thromboplastin synthesis. Liposomes prepared from soyalecithin, containing 60* linoleic acid (18:2) had no stimulatory effect by themselves, but enhanced the stimulating effect of LPS up to 10 fold. When the liposomes were added to the blood samples 0,15,30,60 and 90 min after the LPS had been added, a time dependent response of the liposomes was seen. Blood samples incubated with LPS for 2 hours but only exposed to liposomes for 30 min had monocytes with a thromboplastin activity of 30x10/10-3cells as compared to an activity of 152x10 /10-3 cells in the monocytes of blood incubated with LPS and liposomes for 2 hours. Although the linoleic acid (18:2) is metabolized to arachidonic acid (20:4), it may be more likely that the effect of liposomes is exerted by a mechanism whereby the fatty acid 18:2 is preventing arachidonic acid from being reacylated. This will cause more 20:4 to be free and metabolized to give products required for monocyte activation.A tremendous difference in response to monocyte stimulation between different individuals has been observed. Recently we found that this phenomenon could partially be explained by very active platelets in those with high cell stimuli response. Thus, when platelet rich plasma (PRP) from a high responder was incubated with white cells from a low responder followed by incubation with LPS, there was a drastic increase in monocyte response as compared to the samples where PRP from the low responder was incubated with white cells of its own plus LPS. PRP from a low responder combined with white cells of a high responder resulted in a low response of the monocytes to LPS stimuli.It is concluded that fatty acids and the activity function of platelets may play a central role in monocyte function.
ACQUIRED FACTOR X DEFICIENCY IN MULTIPLE MYELOMA:A COMPLETE RESPONSE TO CHEMOTHERAPY.
Authors: Kos M , Geibler K , Ratheiser K , Pabinger I , Korninger Ch , Lechner K 
Published: August 2018

A 64 year old women without any previous history of bleeding diathesis presented with bone pain and gastrointestinal bleeding. An isolated severe factor X deficiency (factor X activity 0.5%, factor X antigen less than 12.5%) was found. No inhibitor that inactivated factor X in vitro or interfered with factor X assay could be demonstrated. Substitution therapy with a prothrombin complex preparation containing factor X (PPSB Biotest) was given. Factor X recovery in the first 2 days was lower than expected (below 20%) and half life of factor X was shortened (150 minutes). Subsequently, a diagnosis of multiple myeloma (light chain myeloma, type kappa) was made. Amyloidosis was excluded by electronmicroscopic examination of rectum biopsies. Chemotherapy according to the M2 protocol (Case et al) was initiated. Factor X recovery improved dramatically within 2 weeks and there was a continuous increase of factor X activity and antigen during chemotherapy. After 6 courses a complete haematological remission (less than 5% plasma cells in the bone marrow, disappearance of light chains) was obtained and factor X activity and antigen returned to normal.Isolated factor X deficiency is a wellknown complication of amyloidosis. To our knowledge, this is the first case of factor X deficiency in multiple myeloma without amyloidosis. The complete normalization of factor X after successful chemotherapy indicates that plasma cell proliferation may have been the cause of the factor X deficiency. Binding of factor X to plasma cells containing light chains could be a possible explanation, and we are currently examining this hypothesis.
HOMOZYGOUS FACTOR XII CONGENITAL DEFICIENCY: STUDY OF 10 NEW FAMILIES.
Authors: Castaman G , Rodeghiero F , Ruggeri M 
Published: August 2018

Sporadic cases of thromboembolic events have been reported in patients with congenital factor XII deficiency and a relationship with a reduced intrinsic fibrinolysis has been suggested.We report here the results of clinical and laboratory investigations in 10 new families comprising 15 homozygotes (age 16-72) and 14 heterozygotes (age 18-65).In homozygotes, kaolin-activated-PTT was indefinitely prolonged and F XII activity and antigen were undetectable, whereas functional assays . of high molecular weight kininogen ahd kallikrein yielded normal values. Intrinsic fibrinolytic activity - assayed on fibrin plate by measuring lysis zones determined i. by euglobulin fraction, obtained in presence of dextran sulphate and flufenamate (Blood activator inventory test, Kluft 1979) - was reduced in all homozygous pts. to about 50% of normal (range 15-70%; normal range 80-120%); normal values were observed in all heterozygotes. Basal extrinsic fibrinolytic activity (measured after addition of Cl-inhibitor) was absent or minimal as in normal controls. None of our patients showed evidence of thrombotic diathesis.In conclusion, our study demonstrates that a reduced intrinsic fibrinolysis, as assayed by blood activator inventory test, is a common finding in F XII deficiency. The absence of thrombotic diathesis in our cases suggests that, this defect is probably devoid of any clinical significance.
ANTITHROMBOTIC PROPHYLAXIS THROUGH MODIFICATION OF FIBRIN NETWORK STRUCTURE:A NEW APPROACH.
Authors: Dhall D P , Shah A G , Nair C H 
Published: August 2018

Morphometric analysis of electron micrographs have demonstrated that diameters of fibrin strands follow a bimodal distribution comprising a major network of thicker fibres with a minor network interspersed and made up of very fine fibres. The relationship between the two networks is not fixed and invariant. It will be shown that the two networks are highly responsive to changes in the physiological conditions of clotting. Such a system has biological adaptability and tends to result in fibrin which is more suited to serve its varying roles in haemostasis, in limiting sepsis, in promoting neovascularization and in acting as a scaffolding for wound repair.The response of the two network system to dextran, an agent widely used and well known for its antithrombotic properties, has been examined. It will be shown that in vitro dextran increases fibrin fibre thickness, reduces permeability and tensile strength of networks developed in plasma. Similar changes were found to follow when dextran is infused in clinical dosage in man. It was found that the increase in the thickness of major network fibre is at the expense of protein in the minor network. Such means of modulating distribution of fibrin fibre diameter within fibrin networks provide a new approach to antithrombotic prophylaxis.
SPECIFICITY OF MONOCLONAL ANTIBODIES (MABS) TO FIBRINOGEN/FIBRIN MOLECULE USING THE AVIDIN-BIOTIN IMMUNOPEROXIDASE STAINING OF FROZEN SECTIONS OF HUMAN FIBRIN
Authors: Houranieh A , Kudryk B , Davis G L , Ito R K , Statland B E , Yunis E J 
Published: August 2018

To study the effect of Factor XHIa mediated cross-linking of fibrin on the specificity of MAb/TD-1 (specific for the D-dimer of the DD/E region of human cross-linked [XL] fibrin, MAb/T2Gls (specific for the amino terminal region of β chain, β 15-42 and Fibrin II [ des AABB fibrinogen ]) and MAb/l-8C6 (specific for fibrinogen, Fibrin I [ des AA fibrinogen ] and B8 1-42) an Avidin Biotin Immunoperoxidase staining of frozen sections of human fibrin was used. The three monoclonals were applied as first antibodies in the Vectastain ABC Kit ( Vector Laboratories, Burlingame, CA ). Clots were prepared from Imco fibrinogen using 0.015 M Na2HPO4, 0.075 M NaCL, pH 6.35. Where applicable, EDTA 0.01 M was used in the buffer. Bovine thrombin 1 u/ml was added and the clots were incubated overnight at 20°C. Frozen sections were prepared and stained. Kabi grade (L) fibrinogen was also used, but failed to clot in the presence of EDTA. The results of the comperative study were as follows:The positive reaction with T2Gls in both clots preparations is due to the presence of the. neoepitope in cross-linked and noncross linked Fibrin II. The specificity of TD-1 for cross-linked fibrin is supported by a positive reaction in the normal clot, while the reaction was very weak in the presence of EDTA. Due to the cleavage by thrombin of Bβ (Argininel4-Glycinel5) MAb/l-8C6 was negative in both clots. These results indicate, that the Avidin-Biotin Immunoperoxidase staining of frozen sections of human fibrin, is useful for the evaluation of monoclonal antibodies specificity to fibrinogen/fibrin molecule.
THE SIGNIFICANCE OF VON WILLEBRAND FACTOR ANTIGEN (vWFAg) AS AN ENDOTHELIAL MARKER DURING HAEMODIALYSIS
Authors: Rylance P B , Gordge M P , Dood N J , Weston M J 
Published: August 2018

It has been suggested that platelet activation during haemodialysis (HD) is associated with damage to the endothelium which might contribute to increased atheroma seen in HD patients. We have therefore measured vWFAg (by radial immunodiffusion) as an endothelial marker during HD and B-thromboglobulin (BTG) (by RIA) as a marker of platelet activation with various anticoagulant regimes: unfractionated heparin (UFH) (Leo), low molecular weight heparin (LMWH) (Choay CY 216), regional citrate anticoagulation, prostacyclin (PGI2) (5ng/kg/min) and the combination of PGI2 + UFH.Platelet activation occurred (as shown by a progressive rise of BTG) during HD with UFH, LMWH and citrate, but not with PGI2 or PGI2 + UFH. Pre-dialysis vWFAg levels were elevated in HD patients (2.37 ± 1.16 (SD) U/ml) compared with healthy controls (1.15 ±0.34 U/ml, p<0.001). Plasma concentrations of vWFAg increased during HD with UFH (26 ± 13* rise after 120 mins, p<0.001), but not during HD with LMWH, citrate, PGI2 or PGI2 + UFH. UFH infusion without HD did not result in vWFAg rise nor did UFH or IMWH interfere in vitro with the vWFAg assay. Thus PGI2 prevented both platelet activation and release of vWFAg. With IMWH and citrate there was no increase of vWFAg despite evidence of platelet activation.Elevated pre - dialysis vWFAg concentrations in HD patients may reflect chronic endothelial injury or alternatively may be due to impaired clearance of vWFAg in uraemia. The results obtained during HD suggest that vWFAg release occurred only in the presence of both platelet activation and high molecular weight heparin chains. Whether the release of vWFAg reflects disruption and damage to the endothelium or stimulation and displacement of vWFAg remains uncertain.
STUDIES ON THE ROLE OF THROMBOXANE IN THROMBIN-INDUCED PULMONARY INSUFFICIENCY IN THE RAT
Authors: Sandler H , Gerdin B , Saldeen T 
Published: August 2018

The pathophysiology of the acute pulmonary damage that may occur in association with sepsis, hemorrhagic shock and microembolism seems to involve the activity of cyclooxygenase derived arachidonate metabolites. In the rat, pulmonary microembolism due to infusion of thrombin together with inhibition of fibrinolysis has been found to induce pulmonary insufficiency with similarities to the clinical adult respiratory distress syndrome. The infusion of thrombin results in systemic hypotension, pulmonary hypertension and platelet aggregation, and subsequently, with a certain dealy in time, to increased pulmonary vascular permeability.The main purposes of this investigation were to study the release of TxA2 and PGI2 following thrcmbin-induced pulmonary microembolizaticn in the rat and to examine the effects of a thromboxane synthetase inhibitor (DazoxibenR) on pulmonary arterial and systemic mean arterial pressure and vascular permeability.During infusion of thrcmbin in rats pulmonary arterial pressure rose from 15 ± 2 to 35 ± 3 rmHg and mean arterial pressure fell from 120 ± 6 to 49 ± 27 mmHg. Plasma thromboxane B2 (TxB2) increased from 0.3 ± 0.004 to 3.6 ± 0.5 ng/ml. Ninety minutes later the lung weight and albunin concentration in the lung were increased (2.21 ± 0.13 g and 22.7 ± 4.7 mg/g) compared with controls (1.12 ± 0.14 g and 8.5 ± 0.9 mg/g). Dazoxiben reduced the elevated pulmonary arterial pressure and the elevated plasma TxB2 concentration following infusion of thrombin. Ninety minutes after infusion of thrcmbin, the in vitro synthesis of TxB2 in lung tissue was increased. Dazoxiben and a specific rabbit anti-rat neutrophil serun reduced this synthesis of TxB in vitro. The lung weight (2.18 ± 0.20 g) and lung albumin concentration (21.4 ± 3.4 mg/g) was not affected by Dazoxiben. The results indicate that TxA2 in an important mediator of the pressure changes in the early phase after infusion of thrombin and that neutrophils are associated with thromboxane formation in the lung tissue. Rats pretreated with the antineutrophil serum had less pulmonary weight (1.69 ± 0.28 g) and the albumin concentration in the edema fluid was decreased (17.3 ± 3.6 mg/g), suggesting that polymorphonuclear leukocytes contributed to the pulmonary dysfunction. Dazoxiben when incubated with thrcmbin in a chromogenic substrate system had a linear, dose-related anti-thrombin effect. At a Dazoxiben concentration of 2.4 mM only a few percent of the thrombin activity remained.
EFFECTS OF THROMBOXANE PATHWAY ANTAGONISTS ON HEPARIN-INDUCED PLATELET AGGREGATION (H-IPA) AND TESTING FOR HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)
Authors: Brace L D , Fareed J , Hoppensteadt D 
Published: August 2018

We have reported that heparin and heparin fractions can induce platelet aggregation (PA) in a substantial number of normal healthy drug-free donors. H-IPA was shown to depend upon the molecular weight and concentration of the heparin preparation used, but its mechanism remains unknown. Therefore, we performed experiments with antagonists of the thromboxane pathway to determine whether arachidonic acid metabolites contribute to H-IPA. When indomethacin or 13-azaprostanoic (a thromboxane receptor anatagonist) was added to the PRP of donors whose platelets had been shown to aggregate in response to heparin, H-IPA was completely inhibited: heparin (bovine or porcine) caused 75% PA, while pretreatment with indomethacin or 13-APA reduced the response to 6%. Similarly, if the same donors ingested 650 mg aspirin 3 hours prior to phlebotomy, the PA response to heparin was reduced to approx. 10%. These results demonstrate that at least part of the mechanism of H-IPA is mediated through thromboxane generation. However, the mechanism by which'heparin stimulates thromboxane production in platelets remains unknown.In some patients, heparin is known to induce an immune response that causes severe thrombocytopenia (HIT) and is associated with arterial and venous thrombosis. Fratantoni, et al. (Blood 45:395-401, 1975) have introduced a PA method for the diagnosis of HIT. We have used a modification of this method to show that the PA observed when heparin is added to a mixture of normal donor PRP and HIT patient’s serum or plasma can be inhibited by antagonists of the thromboxane pathway. When normal donor PRP was pretreated with indomethacin or 13-APA and then mixed with serum from a HIT patient (290 uL PRP:160 uL serum), the PA response to heparin was reduced from 75% to 10% or less. Similarly, if the PRP donors ingested 650 mg aspirin prior to phlebotomy, PA in the HIT test was reduced from 75% to 10% or less. Thus, the interaction of heparin with the antibody and platelets causes thromboxane generation and leads to PA. Cyclo-oxygenase specific antiplatelet drugs and inhibitors of thromboxane generation may be useful in the clinical management of HIT and H-IPA.
VITAMIN K1 IN HUMAN MILK
Authors: Kries R V , Shearer M J , McCarthy P T , Haug M , Harzer C 
Published: August 2018

Fatal vitamin K deficiency haemorrhage has been observed in breast fed babies. Though the incidence of vitamin K deficiency haemorrhage seems to be low in exclusively breastfed babies in Germany, subclinical vitamin K deficiency is by far more common as demonstrated in recent studies. Vitamin K concentrations in human milk are lower than in cow's milk and infant formula, however, nothing is known about the factors determinating the vitamin K1 concentrations in human milk. Vitamin K1 concentrations in human milk were studied during the first five weeks of lactation with respect to a) stage of lactation, b) interindividual differences, c) relationship of vitamin K1 to other lipids, and d) influence of oral supplements of vitamin K1 given to the mother. Milk samples from 9 mothers were collected on day 1,3,5,22,29 and 36 of lactation using standarized techniques.a) Vitamin K1 concentrations in colostral milk, day 1-5 (median 1,8 ng/ml) were significanctly higher than in mature milk, day 22-36 (median 1,1 ng/ml) (Wilcoxon U-Test p< 0,01). These changes during the course of lactation must be considered for estimation of the vitamin K supply in breastfed babies.b) Vitamin K concentrations both for colostral and mature milk were found to vary widely: colostral milk 0,6-4,4 ng/ml, mature milk 0,4 - 2,8 ng/ml.c) For colostral milk regression analyses revealed good correlations of vitamin K1 to cholesterol but none to total lipid and phospholipids, whereas no correlation to either lipid was observed for mature milk. Cholesterol appears to have a role in vitamin K1 secretion into colostral milk.d) Vitamin K1 concentrations of maternal milk were influenced by oral supplements given to the mother. Even with a dose of 100 μ vitamin K1 (similar to the dose which may be ingested with a meal) a twofold increase of the vitamin K1. content of breast milk was observed. These data suggest that mutritional factors may influence the vitamin concentration in human milk. Vitamin K supplements for breastfeeding mothers on vitamin K1 poor diets could improve the vitamin K supply of these babies.