bluuebunny/crossref_metadata_2025_split huggingface dataset:
An IGM Circulating Anticoagulant Associated With Small Cell Carcinoma Of The Lung
Authors: Handorf C R , Ricardo M J , White F L 
Published: July 2018

A 62 year old white female with small cell carcinoma of the lung presented with a prolonged activated partial thromboplastin time (APTT). The patient had no history of abnormal bleeding but previously had pulmonary emboli. Coagulation parameters other than APTT were within normal limits. Pertinent laboratory data included an IgM lambda paraprotein. Dilution studies indicated the presence of a high titer circulating anticoagulant; specific assay revealed marked inhibition of factor VIII (50 Bethesda units). Factor VIII activity was 26% of normal. A purified IgM fraction of the patient’s plasma was obtained by filtration on a Bio-Gel A-1.5m column. When incubated with normal plasma the IgM fraction demonstrated anticoagulant activity by prolonging the APTT.The patient underwent plasmapheresis with albumin and plasma exchange which significantly corrected the APTT. The combination of small cell carcinoma of the lung and IgM paraprotein with anti-factor VIII activity represents an unusual paraneoplastic syndrome; to our knowledge this combination has not been reported previously.
Study On The Probability Of Carriership In Hemophilia A
Authors: Blanco A N , Elgue G E , Canaveri A A Martinez , Novaro S 
Published: July 2018

The aim of this study was to find a reliable method to detect carriers of hemophilia A. Eighteen obligatory carriers, 14 possible carriers, without a family history but with hemophilic son, and 29 normals were studied. The three groups were in the same age range (19 to 47) had no intake of oral contraceptives and the blood samples were taken in the middle of the menstrual cycle. Factor VIII activity (Factor VIII:C) was determined by the one stage method and the Factor VIII-related antigen (Factor VIIIR:Ag) by Laurell’s immunoelectrophoresis.In the first group we confirmed the carrier state in 72.2% (13/18) by discriminant analysis and 88.9% (16/18) on the basis of the ratio of Factor VIII:C to Factor VIIIR:Ag or its logarithmic transformation. In our Laboratory the logarithmic transformation of the ratio showed the least percentage of misclassification so it proved to be more efficient.To arrive to the final statement concerning the probability of being a carrier we combined laboratory data and pedigree information. In 64.3% (9/14) of the possible carriers the analysis of the laboratory data (by logarithmic transformation) increased their final probability of being carriers.
Generation Of Coagulation Factors By The Isolated Rat Liver Perfused With A Synthetic Blood Substitute
Authors: Owen C A , Bowie E J W 
Published: July 2018

Measuring the release of small amounts of a clotting factor from an isolated perfused rat liver is difficult if the perfusate already contains some of the factor. Further, platelet-containing perfusates generate a coagulant activity that may invalidate clotting assays.We have successfully employed a completely synthetic blood substitute for rat liver perfusions. The perfusate is “Fluosol-43” generously furnished by Alpha Therapeutic Corporation. The oxygen-carrying perfluorochemical is FC-43 (perfluorotributylamine) and the substitute for albumin is hydroxyethyl starch. Using the Brauer perfusion technique, we found that rat livers in 5 hours released an average of 2.3% of the normal plasma concentration of prothrombin, 8.4% factor V, 16.2% factor VII, 7.0% factor IX, 3.7% factor X, 28.3% factor XI and 12.3% factor XII. Antithrombin III and plasminogen were also generated.Only minute amounts of factor VIII were released unless serum, cryoprecipitate or cryoprecipitate-free plasma was added; then the yield was 8.8% on average. The more “venom factor” (platelet aggregability with Bothrops alternata venom) added to the synthetic perfusate, the more factor VIII was released.
Platelet Function Changes In Acute Myocardial Infarction
Authors: Strano A , Raineri A , Novo S , Piraino G L , Mazzola A , Traina M , Davi G 
Published: July 2018

Whether the thrombotic component of myocardial infarction is primary or secondary in a given patient, platelet function alterations can influence many mechanism from which depends if the thrombotic lesion grows or sends platelet emboli to the smaller myocardial vessels. Recently in some cases of infarction, coronary artery spasm has been demonstrated angiographically; thromboxanes, vasoconstrictive and platelet-aggregating substances, are released by platelets during myocardial ischemia. The local release of these substances may modify the myocardial cell viability and regional blood flow.The aim of the present study was to investigate changes in platelet function in relation to the time interval after the beginning of the chest pain in 8 patients suffering from acu te myocardial infarction.The following parameters were estimated: plasmatic PF4 and BTG levels, thromboxane B2 formation by platelets stimulated with thrombin, plasmatic levels of thromboxane B2 MDA formation by platelets stimulated with thrombin, platelet sensi tivity to exogenous prostacyclin; factor XIII activity was also determined.The tests showed, in the first three days, an augmented re lease of platelet constituents together with a “platelet exhaustion”, demonstrated by a reduced formation of MDA and thromboxane B2; in the following days the platelets changed to a state of hyperactivity. The platelet sensitivity to pro stacyclin was reduced during the whole period after the onset of the acute myocardial infarction; this provides an additional mechanism involved in increased platelet aggregation.
Platelet Activation During Treadmill Exercise In Patients With Chronic Peripheral Arterial Disease
Authors: Baele G , Bogaerts H , Clement D L , Pannier R , Barbier F 
Published: July 2018

β-Thromboglobulin (β-TG) and platelet factor 4 (PF-4) are specific platelet proteins released during in vivo platelet activation. An increase in PF-4 after exercise- induced myocardial ischemia was reported by Green, L.H. et al.. This observation prompted us to measure β-TG and PF-4 in patients with chronic occlusive arterial disease of the lower limbs and to look for increments during treadmill exercise.
β-TG was measured using the Amersham test kit and PF-4 using the radioimmunoassay kit of Abbott Diagnostics Division. Plasma levels in 28 normal individuals ranged for β-TG from 7 to 39 ng/ml with a mean value of 21.0 ng/ml, for PF-4 from 1 to 19 ng/ml with a mean value of 6.0 ng/ml.
β-TG and PF-4 were measured in 59 patients with chronic peripheral arterial disease before and 5 min. after treadmill exercising till occurrence of claudication. Plasma levels of β-TG before treadmill exercising ranged from 24 to 260 ng/ml with a mean of 77.9 ng/ml, PF-4 levels ranged from 2 to 240 ng/ml with a mean of 30.4 ng/ml. These levels were significantly higher than those measured in normal individuals.After treadmill exercise β-TG levels showed a statistically significant increase to a mean value of 87.3 ng/ml but PF-4 did not rise significantly (mean value : 32.4 ng/ml). The supplementary increase of already elevated β-TG levels may be explained by enhanced in vivo platelet activation during treadmill exercising till occurrence of claudication. As the clearance of PF-4 from human plasma has been shown to be much faster than the clearance of β-TG increases in PF-4 levels may be more difficult to detect during dynamic explorations of the vascular system.
Correlation Of Platelet With Clinical Studies In Patients With Coronary Artery Disease Pre And Post Coronary Artery Surgery
Authors: Doyle D J , Chesterman C N , Cade J F , Morgan F J 
Published: July 2018

80 patients with angina were studied preoperatively with measurements of 51Cr platelet survival (PS), plasma PF4 and βTG (RIA), platelet aggregates and platelet count. Clinical data was recorded prospectively. 58 patients were restudied a mean of 34 weeks postoperatively, 44 of whom entered a double blind randomized trial of sulphinpyrazone.Mean preoperative PF4 and βTG were elevated above normal values (PF4 14 vs 8ng/ml, βTG 54 vs 32ng/ml) and the mean PS shortened (150 vs 174hrs). These tests returned towards normal postoperatively (PF4 10ng/ml, βTG 39ng/ml and PS 186hrs). This trend is partly due to a significant change in βTG, PF4 and PS in patients treated with sulphinpyrazone.A significant negative correlation was detected between platelet count and angina grade (r = -0.30, p< 0.001), number of previous transmural myocardial infarctions (r = -0.36, p< 0.001) and angiographic grading of severity of coronary artery disease (r = -0.28, p<0.05). No other significant correlation of platelet studies with coronary artery disease (CAD) status was detected. There was however an association between elevated PF4 and βTG and shortened PS in the 4 postoperative patients with peripheral vascular disease (PVD) compared to those without PVD (mean PF4 21.8 vs 7.3ng/ml, βTG 98.1 vs 34.2ng/ml). In addition βTG was negatively correlated with postoperative (not preoperative)triglyceride concentrations (r = -0.73, p< 0.05) which were also correlated with PS (r = 0.72, p< 0.05).Abnormalities in platelet parameters are present in patients with CAD but they do not appear to be sensitive indicators of CAD severity and may well be affected by other factors for example extent of atheroma elsewhere, serum lipids and preoperative stress.
Platelet Survival Time In Men With Post Myocardial Infarction And Normal Coronary Arteriogram
Authors: Casals F , Castillo R , Alfonso L , Vidal J L , Paré J C , Betriu A 
Published: July 2018

Some patients fail to show any evidence of arte riographic coronary obstruction following an episode of myocardial infarction. This type of subjects would all present a shortened mean platelet survival.Over a year’s period, platelet survival time (Chromium 51 labelling)was measured in 8 subjects who, one month after suffering an acute transmural infarction, were found to have a normal coronary arteriogram (NC). Survival times were determined between 3 and 12 months after the infarction. At this moment, all the patients were asymptomatic.As control, and simultaneously, platelet survival time was evaluated at random in 8 patients who had had a myocardial infarction with arteriographic evidence of coronary obstruction (AC), and in 11 normal subjects (NS).Platelet life span was measured by fitting the gamma fonction at 11 days of survival experimental points and the goodness of fitting surveyed by a graphic terminal (Tektroniks 4051). Since a failure of fitting with this system was found in 30% of cases, the mean weight method of computting platelet life span had to be employed.The results of the mean platelet survival time in the three groups of individuals show no significant differences : NS 7,76 ± 0,89; NC 7,48 ±1,68 AC 7,64 ± 0,87 (days ± 1 SD). Only two patients with normal coronary arteriogram had values lower than the inferior range of normal subjects.These results do not agree with others.
Abnormal Platelet Serotonin Uptake And Binding Sites In Myeloproliferative Disorders
Authors: Caranobe C , Sié P , Nouvel C , Laurent G , Pris J , Boneu B 
Published: July 2018

We previously shown that the platelets of patients suffering from myeloproliferative disorders (MD) present not only a reduced capacity to store serotonin (5 HT) in their dense granules but also a dramatic reduction in the initial velocity (Vi) of 5 HT uptake ; this suggests that the abnormalities are not restricted to the dense granules but involve the transport mechanism accross the platelet membrane.The present study concerns the 5 HT binding sites of MD platelets which present such a reduction of the Vi Max (Li- neweaver-Burke plot) of the 5 HT uptake. Binding assays were performed according to the method of Schik et al. (Biochem. Pharmacol. 1979, 28, 2667). Schatchard plot analysis of the binding data revealed two binding sites both in normals and patients : site A with a high affinity and a low capacity and site B with a low affinity and a high capacity.Thus the abnormal 5 HT transport accross the plasmatic membrane is the consequence of a quantitative reduction of the 5 HT binding sites and not of a qualitative defect of these sites. Nevertheless, in spite of the reduction of the number of binding sites, 5 HT-induced platelet aggregation was found normal in these patients.
Itanoxone, An Inhibitor Of Cyclo-Oxygenase, Acts Preferentially On Platelet Than On Vascular Enzyme
Authors: Villa S , DeLhon A , Palmier C , Livio M , Maynardier B , Lauressergues H , de Gaetano G 
Published: July 2018

Several attaints have been made to dissociate the inhibitory effects of aspirin on platelet and vascular cells, but no definite results have been obtained. Other drugs, presumably acting on cyclo-oxygenase, are therefore being investigated for their relative inhibitory effect on platelet and vascular prostaglandin synthesis.The present study was performed in male CD-COBS rats. Itanoxone [ (chloro-2' -diphenyl) -4-oxo-4 methylene 2-butyric acid ], a newly developed, hypolipidemic and hypouricemic compound with moderate anti-inflanmatory activity, showed a short lived, dose dependent (20-200 mg/kg, orally) apparently competitive inhibition of platelet MDA stimulated by either thrombin or arachidonic acid. Repeated doses did not result in any cumulative effect. At doses which completely blocked MDA production, itanoxone also inhibited thrombin-stimulated thromboxane B2 production in platelets but had no measurable effect on vascular prostacyclin generation measured both by a bioassay and a radioimmunoassay of its stable derivative 6-Keto-PGF1α . Pretreatment with itanoxone partially prevented therrhibitory effect of aspirin on both platelet and vascular prostaglandin synthesis. This suggests that itanoxone - like aspirin - acts at the level of cyclo-oxygenase but has much greater selectivity on the platelet enzyme.This pharmacological activity is of great theoretical interest for potential use of this compound as an antithrombotic drug.
Chemiluminescence In Human Platelets
Authors: Würner P , Abtlg F 
Published: July 2018

Chemiluminescence (CL), the formation of malcndialdehyde (MDA) and serotonin release were studied in suspensions of washed platelets in the presence of luminol at 37° C. CL was induced by concanavalin A, A23187, arachidonic acid, thrombin, N-ethylmaleimide (NEM) and thimerosal.Concanavalin A− and the major part of A23187-induced CL was due to leukocytes contaminating the platelet samples. Leukocytes had no influence on CL by the other stimuli.Arachidonic acid evoked two separate signals: the first was peaking at 7 s and decayed within 20 s, while the maximum of the second signal occurred 50 s and returned to the background 70-110 s after its addition. Thrombin induced also two signals, however, with low intensity and with a lag phase of 6 s prior to the onset of the first signal. Exposure of platelets to NEM (≥0.5 mM) lead to a single signal after a lag phase, depending on its concentration, between 20 and 50 s. Thimerosal-induced CL consisted also of a single signal peaking after 35-120 s.ASA and indomethacin prevented CL, formation of MDA and release promoted by NEM or thimerosal. They interfered with MDA-generation and the first signal of CL induced by arachidonic acid or thrombin. ASA and indcmethacin enhanced and NEM (50 μM) suppressed the second siqnal of CL induced by arachidonic acid or thrombin.It is concluded that CL promoted by NEM and thimerosal as well as the first signal induced by arachidonic acid or thrombin depends on prostaglandin synthesis. The second signals indicate arachidonic acid turnover by lipoxygenase. Sulfhydryl reagents such as NEM interfere with platelet lipoxygenase resulting in only one signal of CL. Measurement of CL offers a useful tool with the advantage to allow monitoring of the time course of prostaglandin synthesis and lipoxygenase pathway in intact platelets.
Methods To Evaluate Endothelial Injury
Authors: Bondjers G , Hansson G , Bylock A 
Published: July 2018

During the last decade the potential significance of endothelial injury for the development of atherosclerosis has been subject to an increasing interest. Thus, the effects on the arterial tissue of different types of experimental injury have been thoroughly described. Nevertheless, the hypothesis of a relationship between endothelial injury and atherosclerosis seems difficult to accept unless the effects of any of the well established risk factors for atherosclerosis can be attributed to modulations of endothelial integrity. To evaluate the presence of endothelial injury with light microscopy we have used dye exclusion tests and immunohistochemistry to detect intracellular IgG. The distribution of injured endothelium with these methods appears to be the same, and both methods are well suited for quantitative purposes. As a complement to these methods, 3H-thymidine incorporation and autoradiography may be used as an indirect measure of endothelial injury. On the ultrastructural level, scanning electron microscopy or transmission electron microscopy possibly combined with immunohistochemical techniques may be used. In our hands, however, none of these methods appear very well suited for quantitive assessment of endothelial injury. Nevertheless, dye exclusion tests, immunofluorescence, thymidine incorporation, scanning and transmission electron microscopy together constitute a reasonably complete battery of methods to evaluate the possible relationship between different risk factors and endothelial injury.Using this battery of methods we have observed an increased prevalence of endothelial injury in the vicinity of branching points as well as in the periphery of atherosclerotic lesions induced with hypercholesterolemia. Both these locations show a relationship to the formation and growth of experimental atherosclerotic lesions.
Role Of Endothelial Integrity In Atherosclerosis
Authors: Schwartz Stephen M , Gajdusek Corinne M , Reidy M A 
Published: July 2018

The current view of the pathogenesis of atherosclerotic lesions stresses loss of endothelial integrity as a major event leading to the three major events in lesion formation. ..accumulation of smooth muscle cells, accumulation of lipid and accumulation of platelets. Recent advances in endothelial biology, however, suggest that frank denudation may not exist. Our kinetic studies of small wounds to endothelium both in vivo and in vitro demonstrate the ability of the endothelium to rapidly replace desquamating cells. Furthermore, these small areas of mechanical denudation do not stimulate smooth muscle proliferation. Finally, careful studies of hyperlipemic and hypertensive animals have failed to demonstrate any actual denudation.The possibility remains that denudation occurs repeatedly, with extremely brief periods of subendothelial exposure. Thus lesion formation could represent the cumulative record of multiple, tiny incidents. This hypothesis is, however, difficult to test. Less dramatic forms of injury which may be of interest include alterations of endothelial cell functions in replicating cells as well as alterations in function which may occur independent of any cell loss. This last category receives new emphasis today because of the rapid increase in the number of functions identified in endothelial cells. These include the apparent ability of endothelial cells to synthesize a growth factor which can stimulate smooth muscle proliferation in the absence of the platelet derived growth factor.This work was supported by NIH grants: HL-03174. HL-18645, HLC-7312 and a grant from the R.J. Reynolds Industries, Inc. Dr. Schwartz is an Established Investigator of the American Heart Association.
Mechanisms Of Viral-Induced Endothelial Injury
Authors: Friedman H M 
Published: July 2018

We examined the role of common human viruses as inducors of injury to human umbilical vein or bovine-thoracic aorta endothelial cells grown In vitro. Indicators of infection included endothelial cytopathology, viral replication and viral antigen detection by immunofluorescence. Herpes simplex, adeno, measles and parainfluenza viruses infected both human venous and bovine aorta cells. Mumps, polio, and echo 9 viruses grew only in human venous cells, while coxsackie B4 replicated only in bovine aorta endothelium. Several viruses (CMV, influenza A, RSV) infected neither type of endothelial cell.We examined one virus, herpes simplex type 1 (HSV) in some detail and showed that HSV can establish a persistent infection of bovine aorta endothelial cells in vitro. When HSV was inoculated at a multiplicity of infection (MOI) of 0.1, the amount of infections virus produced by the culture fluctuated over a 3 month period. By the third week after inoculation the endothelial monolayer had recovered and no infectious virus was detected for an additional 2 months. However, by the third month, typical herpetic changes reappeared, 103 plaque forming units of intracellular and supernatant virus was detected, and by infectious cell center assays, approximately 1% of cells produced virus.In separate experiments, human umbilical vein endothelial cells were inoculated with HSV (MOI of 1.0) and examined for induction of surface receptors for the Fc portion of IgG and for C3b. Using 51Cr-labeled sheep erythrocytes coated with IgG or with IgM and purified complement components (C1, C4, C2, C3) an Fc and C3b receptor were detected on the infected cells. These receptors were distinct from one another as demonstrated by blocking experiments using purified Fc fragments, and consisted, at least in part, of viral antigens since antibody to HSV blocked function of both receptors.These studies demonstrate that viruses can produce acute or persistent infection of endothelial cells and can induce receptors for IgG and complement on the cell’s surface.
Triais And Tribulations In The Prevention Of Myocardial Infarction
Authors: Mitchell J R A 
Published: July 2018

“There is no present or future - only the past happening over and over again, now” (Eugene O’Neill).When coronary thrombosis was thought to be clotting in the wrong place, it was assumed that coumarin anticoagulants would modify it, and would prevent myocardial infarction and death. Early trials did not reoognize that sudden deaths and deaths from pump failure and dysrhythmia soon after infarction were not thrombotic events. Bad design, emotive opposition and therapeutic greed led to disillusionment with anticoagulation.The next belief was that thrombosis was haemostasis in the wrong place, so the recognition that dipyridamole, sulphinpyrazone and aspirin modified platelet behaviour led to the hope that these agents would be anti-thrombotic. Our present inability to confirm or deny this shows that our inept handling of anticoagulants has not enabled us to avoid similar problems with these first-generation platelet modifying agents and the problems posed by ART, AMIS and PARIS will be discussed.finally, the newest theoretical concept is that thrombosis is due to TXA2/PGI2 imbalance, so mini-dose aspirin is being suggested as an antithrombotic while we await the arrival of thromboxane synthetase inhibitors, stable PGI, analogues or TXA2 receptor blockers which are being hailed as antithrombotic agents for the future. Unless we show that We have learnt how to test for coronary anti-thrombotic activity we shall be as confused about these new agents in 20 years as we are about the old ones.Meanwhile, the anticoagulant flame has been kept alight in Holland and the results of their trial in patients over 60 and many years after an initial infarction will be described. If the original idea that thrombosis was clotting in the wrong place is correct shall we soon be saying ‘Come back anticoagulants, all may yet be forgiven.?