bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF MOLECULAR WEIGHT ON THE RELATIVE BIOAVAILABILITY OF HEPARIN
Authors: Emanuele R M , Fareed J 
Published: June 2019

Three fractions of different molecular weight (M. W.) were obtained from gel-filtration of porcine mucosal heparin. These fractions along with unfractionated and a low M. W. heparin (CY 216) were compared for relative bioavailability in primates (Macaca mulatta: n = 5). The M. W.'s of all fractions were determined using high performance liquid chromatography - gel permeation and characterizied in terms of mean M. W., peak M. W. and M. W. distribution. Area under the plasma concentration time curve (AUC) was calculated by the trapezoidal method after intravenous and subcutaneous administration and used as an index of bioavailability. For the AUC calculations, plasma heparin concentrations were determined using a Xa/IIa clotting assay (Heptest) and individual callibration curves. Using the AUC data, relative bioavailability was calculated using the following formula:Bioavailability = subcutaneous AUC / dose intravenous AUC / dose Significant differences in the bioavailability of the various molecular weight fractions were observed and inversely related to M. W. The highest M. W. fraction (23,000) showed the least bioavailability at 3 %. The bioavailability of the 13,300 M. W. fraction was 9 % while the 5,100 M. W. fraction was 93 % bioavailable. CY 216 (M. W. 5,400) displayed a relative bioavailability of 88 % while unfractionated heparin (M. W. 12,600) was 40 %. The apparent discrepancy in the bioavailability of the unfractionated heparin is likely due to differences in molecular weight distribution.These studies suggest that the M. W. of heparin preparations influences the relative bioavailability. Heparins of lower M. W. exhibit greater relative bioavailability compared to high M. W. preparations. Furthermore, characterization of both mean M. W. and M. W. distribution are necessary for predicting the bioavailability characteristics of heparin. The relationship between relative bioavailability and the M. W. of heparin may help identify low M. W. heparins as a more efficient agent for subcutaneous regimens in the prophylaxis of venous thrombosis.
LOW DOSE HEPARIN PROPHYLAXIS IN HIP FRACTURE SURGEY -HEPARIN EFFECT; INHIBITORS; FIBRINOLYSIS AND INCIDENCE OF DVT
Authors: Kußmann J , Spannaql M , Boehnke J , Kückel-haus H G , Schramm W 
Published: June 2019

In a prospective studie 129 patients with hip fracture surgery under LDH-prophylaxis (3x5000 U Na-heparinat) were examined in order to find an answer tothe question, if there is a correlation between inhibitor activity, parameters of fibrinolysis, plasma heparin activity and the incidence of DVT.100 patients with ascending phlebography on day 7 to9 post op. were taken into final consideration (blood collection on admission and on day 1, 2, 4, 7 after surgery):1)Incidence of DVT : 17 %.2)Inhibitors: No difference between patients with and without DVT with respect to AT III activity and prot. C concentration ( prot. C activity in progress).3)Fibrinolysis: Elevated levels of DD-fragment (x = 1 780 mg/ml), t-PA Inhibitor (x = 31 AU) and fibrinogen (417 rng/dl) before operation due to preceding trauma. No significant difference between t-PA, t-PA inhibitor and antiplasmin with respect to DVT. Whileplasminogen concent was significantly increased in patients with DVT on day 4 and 7, DD-fragments had lower values on day 7 (x = 1395 / x = 2140 ng/ml).4)Heparin effect: Plasma heparin activity was assesed by an amidolytic anti ll^assay. Although plasmaticheparin action only represents one aspect of thromboprophylactic heparin-activity, there is an obvious difference between patients with and without DVT withrespect to plasmatic heparin activity( p <0.005).
PREDICTION OF POST-OPERATIVE DVT BY SALINE DILUTION
Authors: Chayen D , Blair S D , McCollum C N , Greenhalgh R M 
Published: June 2019

Clinically, it is difficult to predict deep vein thrombosis (DVT), but the in vitro saline dilution test using the Thrombo-elastograph (TEG) is reported to identify the risk for individual patients [1]. The Biobridge Impedance Clotting Time (ICT) is more sensitive and reproducible than the TEG [2], and we therefore studied 33 patients undergoing elective laparotomy to see if pre-operative saline dilution tests using both the TEG and ICT predicted post-operative DVTs. Post-operatively, both legs were scanned daily for 7 days using 125I Fibrinogen to detect DVTs.The mean age of the patients was 65.7±2.4 years and 17 had malignant disease. In this clinically high risk group, 24 developed a DVT.Fifty-one percent were predicted correctly by TEG. The ICT was significantly better as a predictor with 79% of all patients correctly predicted (p<0.01).The saline dilution test using the ICT is a significant improvement on the TEG, and may enable us to tailor DVT prophylaxis policy to each patient’s specific requirements.Heather BP, Jennings SA, Greenhalgh RM. The saline dilution test - a preoperative predictor of DVT. Br J Surg 1980; 67: 63-65Blair SD, Menashi S, Samson D, Greenhalgh RM. Can the hypercoagulability of surgery be measured? Br J Surg 1986; 73: 500.
EFFECT OF PIRACETAM ON THE MEAN INTRASPLENIC RED CELL TRANSIT TIME (MST) IN SICKLE CELL DISEASE AND SICKLE CELL THALASSAEMIA
Authors: Ferrant A , Leners N , Gini E K , Osselaerey J P , Sonnet J 
Published: June 2019

The effect of Piracetam on the MST has been evaluated in 3 children with homozygous sickle cell disease, and in 1 child and 2 adults with sickle cell β thalassaemia. The MST was measured using 99 Tern labelled autologous red cells before and during treatment with Piracetam (160 mg/kg/d). Tests for in vitro fi1terabi1ity of red cells were performed and an improvement of the in vitro deformabi1ity was observed in all the patients.A shortening of the MST was also observed :
EFFECTS OF FLOW PULSATILITY ON PLATELET ADHESION TO SUBENDOTHELIUM
Authors: van Breugel Hans H F I , Sixma Jan J , Heethaar Robert M 
Published: June 2019

Platelet adhesion studies in perfusion chambers are generally performed with constant flow rate or with pulsatile flow generated by a roller pump. No information is available about the effect of flow pulsatility in the physiological range. For this purpose we devised a system consisting of a eccentric rotating disc which forces a driver toward a flexible tube. This movement causes a sinusoidal laminar flow component. The effect of this sinusoidal pulse on platelet adhesion was studied with the annulai^perfusion chamber of Baumgartner using umbilical arteries and In-labeled platelets. Conditions used are described below, where γ [1/s] is the constant flow component, γ0 [1/s] is the amplitude of the sinusoidal component and f [beats/min] is the frequency of the pulse (70 beats/min standard). Adhesion values are expressed as 105 III In platelets/cm2 (n=4).When osciallatory flow (abence of constant component) was generated, platelet adhesion incersed with increasing amplitude of the pulse.These data indicate that pulsatility as persent in the the aorta and large arteries has no effect on platelet adhesion.
COMPARISON OF A MODIFIED BLEEDING TIME/ “HAEMOSTASIS TIME” (HT), WITH THE DUKE AND IVY/TEMPLATE BLEEDING TIMES IN HAEMOPHILIA AND VON WILLEBRAND’S DISEASE
Authors: Janzarik H , Heinrich D , BÖdeker R H 
Published: June 2019

The occlusion time of a Butterfly 25 short cannula inserted into the cubital vein was assessed as a new bleeding time modification. The method excludes the influences of vessel wall and tissue factors since primary haemostasis takes place on the standard surface of the cannula. Avoiding scar formation, the technique can be repeated deliberately. It could be shown that HT correlated better than the Duke and Ivy/ template bleeding times with reduced platelet counts and reflected the effects of aspirin and unfractionated heparin in the same way (Janzarik et al., Blut 1986, 52:345).HT was applied simultaneously with the Duke and Ivy/ template or Simplate bleeding times in haemophilia and von Willebrand's disease (vWD). According to most of the other authors, the skin bleeding times were normal in patients with haemophilia. However, HT was prolonged in 9/16 patients irrespective of the factor VIII:C/IX:C values. The duration of HT correlated significantly to the onset of bleeding symptoms and to the degree of spontaneous bleeding (e.g., haemarthro-ses). In 31 patients with clinically mild or moderate vWD, the Duke bleeding time was prolonged in 3/31 patients, Simplate II in 13/31 patients and HT in 14/31 patients. With the two latter methods, corresponding results were observed in 20 cases, different results in 11 cases. HT and both the other methods correlated significantly to f. VIII:RCo and VIII:C but not to VIII: vWFWe conclude that the repeatable HT method is an interesting diagnostic parameter in haemophilia and vWD. With the Simplate and HT methods simultaneously performed, the influence of vessel wall factors on primary haemostasis may be differentiated.
EVALUATION AND STANDARDISATION OF THE “IN VITRO” BLEEDING TIME TECHNIQUE
Authors: Kratzer MA A , Knedel M 
Published: June 2019

Recently a model of primary hemostasis has been introduced (Kratzer & Bom, Haemostasis 15:357;1985). This in vitro method detects very sensitively pathological platelet functions (Kratzer, Bellucci & Caen, Haemostasis 15:363; 1985). In order to use this technique routinely in the hospital the instrument now called “Thrombostat 4000” has been completely computerized and standardized by Kratzer and von der Goltz, VDG (8221 Seeon, West Germany).An artificial vessel (Aperture: cellulose acetate coated with collagen typ I, 2.2 ug/ mm2) with a single 150 urn hole; capillary: teflon, 200 urn, length 20 mm) was perfused with anticoagulated whole blood (Na-citrate 1 to 10) using a pressure of 40 mbar. To determine the reproducibility of the new technique, in vitro bleeding volume (V), time (T) and flow at the beginning of the experiment (IF), depending on blood viscosity, was measured in a healthy control person at different days (mean +− standard deviation, n= number of experiments).The mean of the intraassay variance (%) was: V (7.1), T(6.8) and IF(3.3). It was possible to measure the mean from day to day with the following variances (%): V(6.2), T(4.7) and IF(4.1). The low variance, which approaches enzymatic determinations is astonishing because platelet cell functions depend on a complex interaction of several thousands of enzymes.The excellent assistance of P. Gossweiler is greatly aknowledged
DETECTION OF LUPUS ANTICOAGULANTS BY THE “INSIDE-OUT MEMBRANE ADSORPTION TEST”: aPTT IS SHORTENED AFTER INCUBATION OF THE PLASMA WITH THE ADSORBENT
Authors: von Felten A 
Published: June 2019

Prolongation of the aPTT in a mixture of a patient’s plasma with normal plasma is characteristic for the presence of a coagulation inhibitor. Since inhibitors directed against individual blood coagulation factors differ in their clinical significance from a lupus anticoagulant (LA), a fast and reliable distinction from each-other would be highly desirable. The test presented which is based on the absorption of antiphospholipid antibodies by use of a stable phospholipid adsorbent largely fullfills this demand.Method 1. Preparation of the LA-adsorbent (modified acc. to Steck et al., Science 168:255, 1970): Fresh human RBC (bl. gr. 0, in 0.5% EDTA) are washed (NaCl, 0.15m / phosphate buffer,0.005m, pH8.0) and lysed in phosphate buffer alone. The membranes are washed with the same buffer (centrifugations: 40’000g, lOmin, 4°C) and incubated 60 min on ice in phosphate buffer, 0.0005m. After centrifugation, the sediment is resuspended in an equal volume of buffer (0.0005m, with merthiolate 0.1%), homogenized and centrifuged in portions of lml; the supernatant is carefully removed. The adsorbent, stored at 4°C in capped tubes, is stable for at least three months.2. Performance of test: To 600ul of patient’s plasma mixed with 600ul normal plasma (citrated), 12ul of heparin (501U/ml) are added. 600ul of the mixture are given to the LA-adsorbent, vorte-xed, incubated (room temp., 30min) and centrifuged (40’000g). From the supernatant as well as the not adsorbed portion of the plasma mixture, heparin is eliminated by adding ECTEOLA-cellulose. After centrifugation, aPTT is determined in both supernatant samples. Results The test is positive, i.e. LA is present, if aPTT is shortened by at least 5 sec after treatment with LA-adsorbent. *not diluted; other samples are mixed 1:1 with normal plasma
HIGH INCIDENCE OF CARDIOLIPIN-BINDING ANTIBODIES IN PATIENTS TAKING ORAL ANTICOAGULANTS
Authors: Koutts K , Exner T 
Published: June 2019

It is known that patients with thrombosis in autoimmune disease often suffer recurrent thrombotic episodes on withdrawl of oral anticoagulants, frequently have raised ACA and may require long term therapy. In view of the association between lupus inhibitors, phospholipid binding antibodies and thrombotic episodes we investigated a broad group of patients (n=140) taking oral anticoagulants for anti-cardiolipin antibodies (ACA).The incidence of raised ACA (defined here as more than 5 S. D. above normal) was 10%, in comparison with less than 2% in both healthy volunteers and randomized hospital patients. Analysis of patients with raised ACA indicated an approximately equal distribution among those with artifical valves and patients treated for thrombotic episodes. ANF and DNA binding studies were negative in most cases and a lupus inhibitor (KCT mixing test) was detectable only in 1/15. APTT/PT ratios were not significantly high in comparison with other clinic patients. The-ACA were predominantly IgG (12/15) in contrast to those fpund in females with recurrent abortions which are frequently IgM's. The binding antibodies appeared to be much weaker in the presence of calcium than in phosphate buffered saline.The patients having high ACA had no excess thrombotic or bleeding complications during their treatment compared with others in this group. This suggests that thrombotic or occlusive events associated with ACA may be adequately treated with oral anti-coagulants.
FIBRONECTIN, ANTITHROMBIN III, VON WILLEBRAND-FACTOR-ANTIGEN AND THROMBOCYTES DURING SEPTICEMIA, PNEUMONIA, SHOCK AND POLYTRAUMA
Authors: Ziemen M , Fierek M , Francos A , Si nn J , Breddin K 
Published: June 2019

In 56 patients with septicemia (N=10), septic shock (N=10), cardiogenic shock (N=7), bacterial pneumonia (N=6) and polytraumatized patients (N=23) fibronectin, von Wi11ebrand-factor-anti gen (vWF:AG), fibrinogen, antithrombin III (AT III) and platelet count were measured during the first week of illness. Like fibronectin vWF:AG is synthesized in the endothelial cells and is a mediator for platelet adhesion. Decrease of AT III and platelet count are sensitive indicators if activation of haemostasisIn all patients with septic shock on the first day of illness fibronectin was decreased (12.9ଗ.2mg/dl; mean +standard deviation) as well as AI III (55넠%) and platelet count (129 000녶 000/mm ). All patients with bacterial pneumonia showed lowered fibronectin levels on Day 1 (12.2±8.5mg/dl), at the same time AT III and platelet counts were lowered in most of these patients. On the first day of septicemia or polytrauma a slight decrease of fibronectin, AT III and platelet counts were observed: the mean of each of these parameters was below the normal range. During cardiogenic shock fibronectin and platelet counts were normal in all patients. vWF:AG and fibrinogen were elevated in nearly all groups during follow up; 1 week after cardiogenic shock the mean of vWF:AG exceeded 400%In contrast to vWF:AG and fibrinogen there was obviously a similar behaviour of fibronectin, platelet count and antithrombin III, possibly as signs of activated haemostasis. vWF:AG and fibrinogen seem to react independently, no correlation was found between these parameters and fibronectin in severely ill patients
THE DOSE DEPENDENCE OF ENDOTOXIN INDUCED ACTIVATION OF THE PLASMA CONTACT SYSTEM. AN IN VITRO STUDY
Authors: Røise O , Bouma B N , Stadaas J O , Aasen A O 
Published: June 2019

The dose and time dependence of endotoxin induced activation of the plasma contact system was studied in citrated plasma incubated at 37,4 °C. During the first six hours no significant changes were seen. At 12 hours markedly elevated plasma kalli-krein (KK) activity was found in plasma tested with the highest doses of endotoxin (2000 and 200 γg/ml). Corresponding to the elevated KK activity reductions of both plasma prekallekrein (PKK) and functional kallekrein inhibition (KKI) were seen. Hageman factor (FXII) values determined immunologically were also reduced parallel to the decreases of PKK and KKI. Changes in high molecular weight kininogen (HMwK) values were seen as wellIn plasma tested with doses of endotoxin lower than 200γg/ml no sign of activation was seen at 12 hours. At 24 hours, however, increased KK activity and decreased KKI and PKK values were seen in plasma incubated with 20 γg/ml of endotoxin. In test plasma with endotoxin concentrations of 2 and 0,6 γg/ml we found . sign of activation in 7 of 8 test tubes using 2 γg/ml and in 2 of 6 test tubes using 0,6γg/ml. In test plasma with the lowest dose of endotoxin (2,0 γg/ml) and in control plasma no changes in either KK activity, KKI, PKK, FXII or HMwK values were found at 24 hoursThe study shows thaf- endotoxin induced activation of the contact system in citrated plasma is a slow process which is both time and dose
HUMAN PERIPHERAL MONOCYTES STIMULATED WITH ENDOTOXIN IN VITRO SHOWED A FAST PROCOAGULANT ACTIVITY (PCA) ELEVATION AND A LATE ANTIFIBRINOLYTIC RESPONSE
Authors: Engebretsen L F , Kierulf P , Lyberg T , Andersen A B , Gulla M , Joo G B 
Published: June 2019

Septicemia causes severe disseminated intravascular coagulation (DIC). Monocytes may contribute to the DIC process through endotoxin stimulated synthesis of PCA. This study was initiated to evaluate the role of the monocytes in DIC further. Blood was taken from healthy persons. Mononuclear leucocytes (30?o monocytes) in microtiter wells (25.000 monocytes/well) were added 1 ug/ml endotoxin, and kept in culture from 0 to 160 hours. The cells were harvested, and the PCA (thromboplastin), the fibrinolytic activity (urokinase-PA), and the antifibrinolytic response (plasminogen activator inhibitor-PAI) were measured in the cells. Cell activities were assayed with chromogenic peptide substratesIn the stimulated cells the PCA dominated initially, whilst the antifibrinolytic activity was dramatically elevated after about 40 hours. The fibrinolytic response was minimal compared to the rise in the PAI activityIn conclusion, the monocytes favoured DIC development during the 160 hours observation period in our experiment through coagulation factor synthesis and hampered fibrinolysis. This support the hypothesis that the monocytes participate in the DIC process
CHROMOGENIC ENDOTOXIN ASSAYS. - FURTHER METHOD DEVELOPMENT AND PRACTICAL EXPERIENCE
Authors: Nilsson K , Friberqer P 
Published: June 2019

A kit for the determination of endotoxin by using Lumulus lysate (LAL) and a chromogenic substrate has now been available for three years. Here we will summarize the present status concerning its usefulness in the control of parenteral drugs, in hygienic control and in clinical diagnosis.The wide variation of uses, demands considerable work for method adaptation to the various types of specimen and laboratory. Almost all samples have to be pretreated to become compatible with the reagents in the assay. It has also been found to be important to consider variousdemands depending on the number of samples, how fast the answer is wanted, simplicity and accuracy of the assay that is needed as well as equipment available. In some cases a single screening test is required. Then a tube with 100 pi of LAL reagent can be taken from the freezer. The other extreme is the determination of hundreds of samples in each series. Then microplates and suitable readers can be of great help. Several other procedures used on special occasions allowing e.g. wide assay range or low reagent cost will also be presented.Manual and microplate procedures have been found suitable and can be made safe regarding contamination and losses of endotoxin. Single stage and micro methods have been tested and found to work. Data concerning material and laboratory equipment have been collected and are now available.By using a quantitative procedure forthe determination of the small amounts of endotoxin present in most samples, it has been possible to find optimal reaction conditions and to trace various kindsof errors. Procedures for method controland trouble shooting are also suggested.
PROTEIN C AND AT III IN ESSENTIAL HYPERTENSION
Authors: Bielawiec M , Kloczko J , Wojtukiewicz M , Borowska M 
Published: June 2019

Since hypertension is generally accepted as a risk factor for atherosclerosis and, on the other hand, alterations in haemostasis were reported in the disease, we focused our interest on two plasma inhibitors-protein C and antithrombin III, which play critical roles in the regulation of blood clotting process. We studied 19 patients with newly diagnosed essential hypertension at ist and 2ncl degreeof the disease (acc.to WHO criteria). Protein C antigen level was measured by means of ELISA Protein C test (Boehringer Mannheim GmbH).AT III and Factor VIII R:Ag concentrations were measured by rocket immunoelectrophoresis acc.to Laurell using monospecific antisera (Behringwerke AG, Marburg). In comparison with healthy subjects the patients with essential hypertension revealed statistically significant decrease in protein C antigen level (79 t 21% vs 101 ± 16; p≺0.01) and substantially increased F. VIII R: Ag values (174 ± 72% vs 103 ± 33%; p p≺0.01). No significant correlation was found between F. VIII R:Ag and protein C level. The patients had also elevation of AT III concentration ofno statistical significance. Since F. VIII R:Ag is produced and released by endothelial cells its elevated level in patients with hypertension may reflect injuryto the vascular wall. Decreased levels of protein C probably due to its increased consumption observed in the patients may contribute to imbalance in the haemostatic system and promote vascular complications.
PATIENTS WITH MILD ESSENTIAL HYPERTENSION HAVE INCREASED PLATELET SIZE AND RELEASE REACTION ANO SHOW INCREASED RECEPTOR RESPONSE TO INFUSED ADRENALINE
Authors: Lande K , Kieldsen I O S S E , Westheim A , Aakesson I , Hlermann I , Eide I , GiesdaL K 
Published: June 2019

Hypertensive (n = 35) and normotensive {n = 44) men all 42 years old were studied. The hypertensive (HT) had larger venous platelets than the normotensive (HT) (7.46 ± 0.10 vs 7.12 ± 0.09 10-15 1, p = 0.01). Plasma concentration of |3-thromboglobulin (BTG) was increased in arterial blood in hypertensive (40 ± 8 vs 21 ± 2 ug/1, p=0.02) while the venous values were similar in the two groups. Despite similar sampling procedure, the normotensive subjects had markedly higher BTGconcentration in venous compared to arterial blood (p≺0.01) at variance from thehypertensive where the arteriovenous difference in plasma BTG concentration was not present. Adrenaline was infused to 13 hypertensive and 12 normotensive subjects with dose gradually increasing to 0.04 pg/kg/min. Forearm blood flow was measured by strain gauge technique and relative forearm resistance calculated as mean blood pressure divided by flow. Twelve normotensive subjects (control group) received saline infusion.Change in forearm resistance reflectsβ2- activation of smooth vascular cells, change in platelet count reflects splenic liberation of platelets in response to adrenergic stimulation while change in BTG may reflect platelet release upon stimulation of α2 -receptors. Thus, middle aged men with essential hypertension show increased sensitivity to adrenaline infusion in vascular smooth muscle, spleen and platelets.