bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

α1-Antitrypsin (α1-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.
Abnormal Ristocetin-Aggregation of Platelets in Uraemia and on Haemodialysis Therapy
Authors: Woods H.F. , Turney J. , Weston M.J. 
Published: May 2019

Impaired platelet aggregation to ADP and collagen is recognised in uraemia and the loss of normal platelet function contributes to the prolonged capillary bleeding time observed in uraemia. In von Willebrand’s disease prolongation of capillary bleeding time is associated with impaired platelet aggregation to ristocetin because of a relative or absolute deficiency of the Factor VIII-Ristocetin Cofactor. We have studied platelet aggregation to ristocetin and Factor VIII coagulant activity (CA) and related antigen (RA) in 14 uraemic and 28 dialysed patients. Ristocetin aggregation (delta-0.D/min) was significantly less in uraemia (50 ± 21: m ± S.D) and in dialysis patients (38 ± 18) than in controls (78 + 20). Factor VIII CA and RA were significantly higher in uraemic and dialysed patients than in controls.In crossover studies plasma from uraemic patients either enhanced or did not change ristocetin aggregation of normal platelets but plasma from dialysed patients impaired ristocetin aggregation of normal platelets. Plasma from dialysed patients was not contaminated by heparin. Thus in uraemia impaired platelet aggregation to ristocetin is unlikely to be due to a Factor VIII deficiency and may be due to a membrane defect as in Bernard-Soulier disease. In dialysed patients’ plasma there appears to be an additional circulating inhibitor of platelet-ristocetin interaction.
Changes Induced by Venous Stasis on Factor VIII Activities (VIII:C; VIIIR.AG; VIIIR:WF) in Different Clinical Conditions
Authors: Ponari O. , Pini M. , Manotti C. , Dettori A.G. 
Published: May 2019

F.VIII related activities (coagulant-VIII:C, antigen-VIIIR:AG, v.Willebrand factor-VIIIR.WF) before and after venous occlusion (VO) were investigated in pregnant women, in women on the pill, and in men with atherosclerosis obliterans, “ean basal values of atherosclerotic patients were not different from healthy male’controls. A concordant rise in all the three activities was seen after VO in both groups without any change in the ratios between them. Basal values of women on long-term hormonal contraception were also comparable with those of a control group, while a group of third trimester pregnant women showed high values for all components, and very high ones for VIIIR:AG, with striking increases in AG/C and AG/WF ratios. Following VO, strictly concordant variations in the three activities were observed in all cases, so that ratios remained always unchanged, at their different levels.The results are consistent with the hypothesis of a “complete” F.VIII released activity, induced by venous stasis in these conditions. Pregnancy has quite different effects on F.VIII in comparison with estro—progestinic treatment. No variations seem to be associate! with occlusive arterial disease.
Inhibition by Peptidic Fragments of Clq of Platelet - Collagen Interactions
Authors: wautier J.L. , Reid K.B.M. , Legrand Y. , Caen J.P. 
Published: May 2019

Clq (first component of complement) has been shown to inhibit platelet aggregation induced by collagen. Platelet aggregation and adhesion to purified type I or type III collagen have been studied in the presence of various fragment of Clq.The collagen like region was obtained by digestion of Clq by pepsin and by isolation of the fragments by chromatography on sephadex G 200. The globular region was prepared by digestion of Clq by collagenase, and filtration. The collagen like region is as effective as native Clq in inhibiting platelet aggregation or adhesion in the presence of type I or type III collagen, while the globular region was without effect.Using peptides obtained from the collagen like region of Clq (reduction and alkylation, performic oxidation, CNBr treatment, extensive pepsin digestion) it could be shown that the fragment (FR II = 70 Amino Acid) was responsible for the inhibition of the platelet adhesion and aggregation induced by type I or type III collagen.The Amino Acid sequence of this fragment was compared to the known sequence of the collagen peptides involved in platelet adhesion (see Fauvel et al).
Atherosclerosis in Homozygous and Heterozygous von Willebrand Pigs
Authors: Fuster V. , Bowie E.J.W. , Fass D.N. 
Published: May 2019

We have reported that pigs with severe homozygous von Willebrand’s (vW) disease are resistant to spontaneous and high cholesterol diet-induced atherosclerosis. In this study we report the incidence and quantitation of aortic fibrous atherosclerotic plaques in three groups of pigs fed with a high (2%) cholesterol diet from age 3 to 9 months.
Normal pigs (normal factor VIII antigen - VIII R:AG and ristocetin co-factor - VIII:RWF). Of 11 pigs, 8 (73%) had significant plaques involving more than 3% (mean 7.6%) of the aortic surface. Homozygous vW pigs (undetected VIII R:AG and VIII:RWF). None of the 7 pigs had significant plaques involving more than 3% of the aortic surface (p<0.01, rank ≤ test). Heterozygous_vW pigs (approximately 40% VIII R:AG and VIII.RWF). Of the 5 pigs, 3 (60%) had significant plaques involving more than 3% (mean 7.7%) of the aortic surface, the results not being significantly different from those obtained in the normal pig.This study suggests that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This might have implications in man since in human vW disease both factors are almost always present to some degree.
Structure of Heparin and Related Glycosaminoglycans
Authors: Casu B. 
Published: May 2019

The structure of heparin is largely accounted for by disaccharide sequences of α1,4-linked 2-0-sulphated L-iduroic acid and N,6-0-disulphated D-glucosamine. However, the insertion of other residues (especially D-glucuronic acid, nor-sulphated L-iduronic acid and N-acetylated D-glucosamine) leads to hybrid structures. Also the other iduromc acid-containing glycosaminoglycans are structurally heterogeneous. Heparan sulphates contain variable amounts of heparin-like blocks, ana dermatan sulphate contains also chondroitin -like segments.Available evidence on the structure and conformation of the above glycosaminoglycans will be discussed in terms of the availability ot individual functional groups for interaction with plasma proteins.
A Case of Familial Antithrombin III Deficiency in an English Family
Authors: Haas de H.A. , Scully M.F. , Clark S.E. , Kakkar V.V. 
Published: May 2019

In this case a mother and three of her four sons living in southern England are affected. The mother’s At III level measured as progressive At III (chromogenic substrate) was 51% heparin cofactor 61% and by immunological assay 53%. Three sons have At III levels of 48%, 55%. and 56%, (progressive), 43%, 54% and 51% (heparin eofarctor), and 53%, 57% and 51% (immunological) respectively. By a clotting assay the sons were found to have values of 60%, 56% and 63% Crossover immmunoelectrophoresis against At III antisera in the presence of heparin (Sas et al, 1975) showed no difference from normal, distinguishing this form of deficiency from Antithrombin Budapest. A sister of the mother and four other members of the family had normal At III levels. All members of the family had normal levels of α1 antitrypsin and α-2 macroglobulin as measured by the radial immunodiffusion technique.Clinically all the At III deficient sons have had recurrent DVT and have grade IV post phlebitic legs. One son has also had in addition, an inferior vena cava thrombosis (at age of 8 years) and mesenteric thrombosis (at age of 30 years). The development of a thrombosis at age 8 may illustrate that symptoms of At III deficiency may not be confined only 8 adulthood. Affected members of the family are at present: on a regimen of self administered low-dose subcutaneous heparin.
Pharmacological Studies on the Antithrombotic Action of Synthetic low Molecular Weight Inhibitors of Clotting Enzymes
Authors: Markwardt F. 
Published: May 2019

Biochemical investigations allowed the identification of benzamidine derivatives as highly effective competitive inhibitors of clotting enzymes. Their anticoagulant effect is not only based on the inhibition of the thrombin-fibnn reaction, but also on that of thrombin-induced platelet reactions and activation of clotting factors. The inhibitory effect on factor Xa potentiates the anticoagulant action. However, the inhibitors interfere with the antithrombin III reaction.Selected benzamidine derivatives are critically observed from the aspect of their use as antithrombotics. The pharmacokinetic behaviour was studied using radiolabelled compounds. Due to the relatively rapid elimination from the blood repeated administration is required in order to maintain an adequate concentration in blood. Experimental, venous, arterial, and microthromboses in rats could be prevented by infusion of the inhibitors. Their protective effect was dependent on the affinity for the clotting enzymes (Ki-values) and on the blood levels. Synthetic low molecular weight inhibitors of serine proteinases are considered therapeutically relevant compounds.
The Prostaglandin-3 Family and the Prevention of Thrombosis
Authors: Dyerberg J. , Bang H.O. 
Published: May 2019

In the search for the cause of the rare occurrence of ischemic heart disease in Eskimos the interest is focused on cis 5,8,11,14,17 eicosapentaenoic acid (C20:5). C20:5 is not a precursor for proaggregatory prostaglandins whereas vascular tissue can convert it to a potent antiaggregatory substance. Greenlanders in whom C20:5 occurs in high concentrations in the plasma lipids in stead of C20:4 should have a balance between platelet aggregatory and antiaggregatory ability dislocated towards the latter. In a expedition to North-West Greenland during the autumn of 1978 this hypothesis was veryfied.The platelet aggregation after ADP and collagen stimulation and the bleeding time in Eskimos differed significantly from those of age and sex matched Danish controls. Investigations of haemostatic characteristics ruled out other explanations of the prolonged bleeding time and decreased platelet aggregability in Greenlanders.The observations might have great inplications in the prevention of thrombosis, pointing at the possible role of the prostaglandin-3 family.
Effect of Low-Dose heparin and dihydroercotamine prophylaxis on incidence of postoperative deep-vein thrombosis in patients undergoing hip surgery
Authors: Lahnborg G. , Beerman B. 
Published: May 2019

The favourable effect of low-dose heparin prophylaxis in preventing postoperative deep-vain thrombosis (DVT) in patients undergoing surgical treume has bean shown in several investigations. However, there are still some patients sustaining DVT in spite of heparin prophylaxis. In an attempt to improve the prophylaxis, dihydroergotamine (DHE) has been added to the heparin.In a prospective trial the effect of low-dose heparin and DHE prophylaxis was studied in 190 patients undergoing nailing of fractured femoral neck. The patients were divided into 3 groups and were randomly given heparin or a combination of heparin and DHE and the third group was given only saline.The frequency of DVT, detected by the 125-I-fibrinogen method was 167. in the group given heparin and DHE, 20%, in the heparin group and 39% in the control group.Preliminary results. Completed evaluation will be presented during the congress.
Induced Coronary and Aortic Atherosclerosis in Swine with Von Willebrand’s Disease
Authors: Griggs T.R. , Sultzer D. L. , Reddick R.L. , Brinkhous K.M. 
Published: May 2019

Swine with von willebrand’s disease were used to study effects of balloon denudation of coronary endothelium and cholesterol feeding on coronary and aortic atherogenesis. Thirty-two pigs were prepared. Eight were phenotypic normals, 10 were carriers and 9 were bleeders. Coronary narrowing by atherosclerosis (induced by balloon denudation and diet) developed to some degree In all of the pigs. Greater than 50% luminal narrowing of one vessel was present in 6 normals, 8 carriers and in 6 bleeders. Myocardial infarction occurred in 2 normals and 4 carriers. No infarctions occurred in bleeder animals.Aortic lesions (diet-induced) of 3 types were produced: 1) a flat, fatty lesion, 2) a raised, fatty lesion, and 3) a raised, fibrous cap lesion. Every test animal developed lesions of each type. The extent of total raised lesion as per cent of total aortic luminal surface averaged 8.5% in normals, 6.0% in carriers and 5.5% in bleeders.In summary:1) Ballooned coronary vessels developed narrowing of a similar degree la normal, carrier and bleeder pigs. 2) Bleeder pigs developed no myocardial infarction in spite of the presence of coronary disease of the same degree as in careers and normals. 3) Bleeder pigs developed less aortic atherosclerosis in response to cholesterol feeding than did normals and carriers; but no pig was free of lesions.
Prophylaxis Against Postoperative Thromboembolic Complications. A Comparison Between Dextran 70, Dihydroergotamin Heparin and a Sulphated Polysaccarid
Authors: Bergqvist D. , Hallböök T. , Lindblad B. 
Published: May 2019

Dextran 70, a fixed combination of dihydroergotamine and low dose heparin (DHEH) and a sulphated polysaccarid (PZ68B) have been compared for prevention of postoperative thromboembolism. The trial has been prospective with separate randomization of patients undergoing elective general surgery, elective hip surgery and hip frecture surgery. Deep vein thrombosis has teen diagnosed with the 125 I-fibrinogen test. In patients undergoing elective hip surgery pulmonary x-ray and perfusion scintigraphy have been made preoperatively and on postoperative day 7, The patients have been followed for 30 days to detect late fatal pulmonary emboli. 253 patients have been studied -(34 exclusions), the main results being as follows:In conclusion there is a good and equal prophylactic effect against postoperative thrombosis of DHEH and PZ68E in elective surgery, and the two methods are as effective as dextran 70 in hip fracture patients.
Activaed Platelets and Platelet Function in Traumatic, Septic and Hemorrhagic Pre-Shock Conditions
Authors: Ziemen M. , Friedrich I. , Breddin H.K. 
Published: May 2019

Subcutaneous and other tissues contain a lipoprotein which induces instant morphologic platelet changes (sphering and pseudopode formation), which can be evaluated using phase contrast microscopy. Such material might get into circulation in different forms of shock and in pre-shock conditions. Besides measuring the extent of morphologic platelet changes with time after blood sampling the following parameters were investigated at 12-24 h intervals in 13 patients with different forms of shock: platelet-count and -spreading, beta-thromboglobulin, PTT, fibrinogen, thrombin-, reptilase-, and thrombincoagulase-time, fibrinogen degradation products, antithrombin III, heparin cofactor and plasminogen.In patients with septicaemia and septic shock activated platelets were found increased in each case. In other forms of shock and pre-shock the findings were not as uniform. Beta-thromboglobulin was increased during the first phase of traumatic shock with decreasing levels during the following days. Generally the platelet number was reduced and spreading was inhibited. The increased activity of platelets in septic and other shock conditions may be caused by tissue lipoproteins in the circulation.
F VIII R:Ag/F VIII:C Ratio and Beta-Thromboglobulin Levels in Haemolytic-Uremic Syndrome in Children
Authors: Rossi E. , Cossu M.M. , Margstakler E. , Mondonico P. , Tantalo V. , Edefonti A. 
Published: May 2019

Four infants with Haemolytic-Uremic Syndrome (HUS) were investigated sequentially for F VIII R: Ag/F VIII: C ratio, F VIII: C (one-stage method)/ F VIII: C (two-stage method) ratio and beta-thromboglobulin levels. There is a close relationship between the patterns of FVIII R: Ag/F VIII: C ratio and beta-thromboglobulin, as well as between these parameters and the course of the disease. High values of F VIII R: Ag/F VIII: C ratio and beta-thromboglobulin levels were found in the acute phase of the disease and normal values during remission (after treatment with plasma and anti-aggregating agents). Moreover, normal values of F VIII: C (one-stage method)/F VIII: C (two-stage method) ratio (indicating enhanced thrombin production) were always found.These data confirm the prominent role of endothelial damage and subsequent platelets aggregation in the pathogenesis of HUS in children.
Stability Over Time of the Heterozygous VWD Phenotype
Authors: Miller C.H. , Graham J.B. , Goldin L.R. , Elston R.C. 
Published: May 2019

A study has been made of 181 members of two large vWd kindred in the Carolinas. Analysis of the data from first testing showed that the trait, “affected”—meaning abnormal on one or more of 4 tests (BT, VIII:C, VIIIR:Ag, VIIIR:WF)—was transmitted as an autosomal dominant. There were 23, affected members in the smaller (418) kindred, and 57 affected in the larger (750) kindred. Penetrance of the vWd allele was reduced to 58%, and the “affected” phenotype was highly variable, when the tests were scored (+)= normal and (-) = abnormal, 11 of the 16 possible combinations of (+) and (-) were observed. Only 15% of those affected were of the classical phenotype, i.e. abnormal on all 4 tests.A subsample (22 persons) of the larger kindred was re-tested twice, 1½ and 2 years after first testing. The “affected” phenotype was found to be very stable over time. In a total of 140 additional tests only 18 (12%) shifted from “abnormal” to “normal” or vice-versa; and only 5 of 22 persons (23%) shifted class; 2 shifting from “affected” to “non-affected”, 2 from “non-affected” to “affected” and 1 from “affected” to “non-affected” to “affected”.
Inhibition of Thrombin-, Epinephrine- and Collagen-Induced Platelet Aggregation by α1-Acid Glycoprotein
Authors: Andersen P. , Eika C. 
Published: May 2019

α1-Acid glycoprotein (α1,-acid GP) isolated from human plasma was found to inhibit thrombin-induced aggregation of washed human platelets (0.05 NIH U/ml final conc.), and inhibition was complete with physiological concentrations of α1-acid GP (1.0-1.5 g/1 final conc.). The inhibitory effect seemed to occur immediately on thrombin addition, thus similar to the effect of heparin previously observed. As opposed to heparin, however, α1-acid GP did not affect spontaneous platelet aggregation. Furthermore, α1-acid GP (in optimal cone.) reduced the combined inhibitory effect of heparin and antithrombin III on thrombin-induced platelet aggregation, thus consistent with the previous findings using heparin thrombin clotting time.Snyder and Coodley (1976) found α1-acid GP to inhibit platelet aggregation induced by epinephrine and adenosine diphosphate in platelet-rich plasma. As we also found α1-acid GP to inhibit collagen-induced platelet aggregation, α1-acid GP may possibly act as an inhibitor of the release reaction though fairly high concentrations (10 mg/ml final cone.) was needed for complete inhibition.
Factors Influencing Thrombin Induced Platelet Release Reaction
Authors: Hattey E. , Binder B.R. 
Published: May 2019

To study the effect of pH and platelet counts on thrombin induced platelet release reaction, washed human platelets labeled with 14C-serotonin were suspended in phosphate buffered saline of varying pH values for 15 minutes with thrombin concentrations between 1,1 and 0,068 NIH U/ml of suspension. The amount of serotonin released caused by the thrombin added was dependent on the pH of the incubation medium with an optimum in the range of pH 7,4 -7,6. This effect was more marked with higher thrombin concentrations. The serotonin release controles without thrombin were not influenced by the different pH values and were always less than 10%. The amount of platelets in the reaction mixture influenced the release values not significantly at thrombin concentrations of 1,1 and 0,27 NIH U/ml While with 0,068 NIH U/ml a significant dependence of the release on the number of platelets was observed, resulting in higher release values in platelet mixtures with lower platelet counts.Therefore it can be concluded that the pH is of major influence on the release reaction especially at high thrombin concentrations while the platelet count is of importance only at low thrombin concentrations.
Prophylaxis of Deep Vein Thrombosis in Gynecology
Authors: Hohl M.K. , Lüscher K. P. , Gruber U. F. 
Published: May 2019

There is only scarce data regarding the prevention of DVT in gynecology. Trials using 3x5000 IU/day of Heparin s. c. or 2x2500 IU + 0,5 mg Dihydroergotamine (DHE) s.c./day in gynecological patients have not been published. Therefore we conducted a prospective, randomized trial comparing the two regimens.
Methods: Included were patients at the age of 40 or over undergoing major gynecological surgery lasting more than 30 minutes under general anesthesia. The I125-Fibrinogen-uptake test was used in all patients for the diagnosis of DVT.
Heparin administration: 5000 IU Na-Heparin (Roche) were given s.c. 2 hours before the operation and 8-hourly thereafter for 7 days.
Heparin + DHE administration: 2500 IU Na-Heparin +0,5 mg DHE (Sandoz) were given s. c. 2 hours preop. and 12-hourly thereafter for 7 days.
Results: Patients in all groups were well matched for age, bodyweight, duration of anesthesia and type of operation. 2 (31%) of 64 patients receiving Heparin and 4 (6. 6%) of 61 treated with DHE-Heparin developed positive leg scans (p > 0. 3). Major bleeding, complications, massive intraoperative bleeding and reoperation for postoperative bleeding or wound hematoma were found significantly more often in the Heparin group (10.9%) than in the DHE-Heparin-group (1. 6%) (p < 0. 05). Conclusions: One third of the Heparin dosis is as effective as the full dosis when DHE 18 added. The lowering of the Heparin dosis leads to a lower number of major bleeding complications.