bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE VARIATION OF ARACHIDONIC ACID METABOLISM OF PMN LEUKOCYTES IN CEREBRAL THROMBOSIS
Authors: Wang Z , Lehuu B , He Y , Raun C 
Published: August 2018

It was suggested that there is a transfer of metabolites between leukocytes,paltelets and endothelial cells,and that the leukocytes might take part in thrombosis and haemostasis. In order to ascertain whether the arachidonic acid metabolism of PMN leukocytes changes when cerebral thrombosis occurs, we studied this metabolism using isolated human PMN leukocytes, stimulated by ionophor A23187. PGE2 and TXB2 were measured with the method of radioimmunoassay, while leukotrienes(LT) were separated and measured by HPLC. The amount of PGE2, TXB2 and LTs produced by PMN leukocytes of 8 normal volunteers was compared with that of 8 patients suffering from cerebral thrombosis. All these patients were confirmed by CT examination. We found that the production of TXB2, LTB4 and its derivative 20-0H-LTB4 of PMN leukocytes of patients was significantly enhanced. The PGE2 production of PMN leukocytes of patients was also higher than that 0? the volunteers, but without statistically significant difference.These results demonstrate that leukocytes and their arachi donic acid metabolites might play some role in the pathogenetic sequence of cerebral thrombosis. And it is possible that LTB4 is not only a potent inducer of neutrophil chemotaxis and leukocyte aggregation, but also an associated factor in the ischemic vascular disease. It seems that the increasing production of TXB2 and LTB4 by PMN leukocytes is not the main reason of cerebral thrombosis. Hoever, it might accelerate the degree of brain tissue ischemia. We observed that corticosteroids, as an inhibitor of phosphoIipase A2,strikingly reduced the production of arachidonic acid metabolites by leukocytes. Therefore, it is probable that the efficacy of corticosteroids on cerebral thrombosis is, in part, due to inhibit the production of these arachidonic acid metabolites of leukocytes.
ERYTHROCYTES(RBC) AS SUICIDAL ENDOGENOUS SCAVENGERS IN IMMUNE TRIGGERED GRANULOCYTE(PMN)MEDIATED VASCULAR DAMAGE
Authors: Boogaerts M A , Zachée P , Emonds M P , Goossens W , Verwilghen R L , Lins R L 
Published: August 2018

PMN produced toxic oxygen radicals(TOR)have been implicated in the generation of endothelial injury in a number of clinical conditions e.g. in apheresis,hemodialysis, ARDS and atherosclerosis. RBC have shown to inhibit TOR induced damage in a number of hyper-oxic lung injury models.We surmised RBC may serve as endogenous TOR scavengers in those in vivo situations where PMN are immunologically triggered(e.g. complement-activation in hemodialysis)to produce endothelial damage.However, RBC in their role as scavengers may became more vulnerable to further oxydant stress and display a reduced life span.Confluent monolayers of 51cr-labeled human umbilical vein endothelial cells will release 7.5 ± 1.3% of their label upon incubation with complement triggered PMN.When these PMN (l)are premixed with RBC(10),the endothelial damage can be inhibited by 78.4 ± 3.2%.This inhibition can be reproduced by replacing intact RBC by their hemolysates,but not by red cell ghosts.In a 51cr-RBC cytotoxicity system,phorbolester stimulated PMN will lyse 52.6 ± 4.2% RBC.Addition of unlabeled RBC(1/5),inhibits cytotoxicity by 31.1%,their hemolysate by 100%.Pretreatment of added unlabeled RBC with the anion channel blocker DIDS,did not significantly block the scavenger effect.RBC-targets fron hemodialysis-patients(n=8),are more vulnerable to PMN mediated cytotoxicity than normal controls(+24.1%,p<0.001). This vulnerability is further increased(+16.3%,p<0.05)during the early stages of the hemodialysis-procedure,at the time when granulocyte counts are lowest and TOR-generation highest.The GSH of he-modialysis-RBC can be more rapidly depleted upon challenge byAPH, while they also display a significant higher methemoglobin production upon sodium ascorbate challenge,both indicative of their, increased oxidative sensitivity. High dose Vitamin C(10™3M)or desfe-rioxamine(10™3M)inhibit all RBC cytotoxicity.We conclude that RBC serve as endogenous scavengers of TOR,generated by PMN,triggered by corplement activation during hemodialysis. However,by doing so,they became themselves more vulnerable to further oxidative stress,which may contribute to the chronic anemia of hemodialysis-patients.
THE MECHANISM OF THE HYPERCOAGULABLE RESPONSE TO HAEMORRHAGE
Authors: Blare S , McCollum C N , Greenhalgh R M 
Published: August 2018

Gastrointestinal haemorrhage causes a hypercoagulable state and early blood transfusion increases both rebleeding and transfusion requirements [1]. The role of x- and B-adreno-receptors in the mechanism of this hypercoagulable state and the effects of infusions have been studied in NZW rabbits.Haemorrhage was simulated by aspirating 20% of the blood volume from the median ear artery. Coagulation was measured before haemorrhage and at 30-minute intervals using the Biobridge Impedance Clotting Time (ICT). Three different groups of rabbits were used: (a) normal controls, (b) B-blocked with propranolol 1mg/kg, and (c) x- and B-blocked with phentolamine 3mg/kg and propranolol 1mg/kg. Equal volumes of (i) Haemaccel, (ii) fresh blood or (iii) stored blood were then given 30 minutes after haemorrhage.Mean ± sem ICT was 6.0±0.15 minutes before haemorrhage, with no difference between the groups, suggesting that x- and B-blocking drugs have no effect on baseline coagulation. Haemorrhage produced a hypercoagulable state with the mean ICT shortened from 6.1±0.2 to 2,2±0.2 minutes (p<0.01). This response was significantly reduced to 5.2±0.4 and 5.1±0.2 minutes by both B-blockade and combined x- and B-blockade respectively.Haemaccel had no significant effect on the hypercoagulable state, with the ICT going from 2.6±0.2 to 2.8±0.3 minutes. However, fresh and stored blood both reversed hypercoagulability with ICT increasing from 2.6±0.3 to 4.6+0.2 and 5.1±0.1 minutes respectively.In this model the hypercoagulable response to haemorrhage appears to be mainly B- mediated and is partially reversed by both fresh and stored blood, but not by Haemaccel.1. Blair SD, Janvrin SB, McCollum CN, Greenhalgh RM (1986). Br J Surg 73: 783-785.
THE INFLUENCE OF CHEMOTHERAPY ON THE PLASMATIC COAGULATION AND FIBRINOLYTIC SYSTEM IN LUNG CANCER PATIENTS
Authors: Ruiz M A , Marugán I , Estellés A , Espafia F , Aznar J , García-Conde J 
Published: August 2018

Following the administration of cytostatic drugs, an increase in thromboembolic phenomena has been described in cancer patients. Such hemostatic alterations may be related to degree of hipercoa-gulability observed following chemotherapy, in comparison to previous levels. In terms of the fibrinolytic system, however, no - clearly defined alterations have been detected. We studied the - changes in plasmatic coagulation and fibrinolysis in 40 patients with non-operable stage III and IV lung cancer (30 epidermoid - ad 10 microcytic neoplasms) following cytostatic chemotherapy. Two studies were done on each patient, i.e., one at the time of diagnosis, -and the other 48 hours after completing the first chemotherapeutic cycle. The results show significant (p 0,05) post-chemotherapy increases in fibrinopeptide A (FPA) levels (pre: 2.95 ± 3.98, post: 8.15 ± 9.40 ng/ml), as well as a decrease in fibrinolytic activity reflected by a drop (p 0.01) in functional tissue plasminogen activator (t-PA) (pre: 1.53 ± 1.66, post: 0.91 ± 0.95 ng/ml). Morever, a tendency towards reduced euglobulinic precipitate lysis on fibrin agar was observed (pre: 122.8 ± 85.7, post: 105 ± 71.5%). The other parameters evaluated, i.e., antithrombin III, plasminogen immunologic t-PA and functional PA inhibitor - (PAI) showed no significant changes.We have also studied the potential accumulative effect of three chemotherapy courses and the results were compared to the situation at the time of diagnosis. A significant increase p 0.01 in functional PAI has been observed (pre: 1.85 ± 2.38, post: 5.41 ± 3.74 U/ml). The possible participation of tumor mass in the elevation of these parameter was considered: but no relation betwen tumor mass and increase PAI have been detected.Chemotherapy is apparently capable of conditioning a decrease in fibrinolytic activity in these cancer patients, this could be related to the enhanced tendency of these patients to developing - thromboembolic phenomena following cytostatic chemotherapy.
ALTERATIONS IN COAGULATION AND FIBRINOLYSIS IN LUNG CANCER PATIENTS
Authors: Ruiz M A , Estellés A , Marugán I , Navarro I , Aznar J , García-Conde J 
Published: August 2018

Lung cancer has commonly been associated with to both clinical problems of thromboembolism and to biological alterations in -coagulation and fibrinolysis.We evaluated some coagulation and fibrinolytic parameters of the plasmatic coagulation and fibrinolytic system (Fibrinopeptide A (-FPA-) for enzimoimmunoassay, immunological tissue plasminogen activator (t-PA) for enzimoimmunoassay, functional (t-PA) for -chromogenic substrate and functional t-PAinhibitor (PAI) in 40 non-operable lung cancer patients (Table I) comprising 39 males and one female, aged 45 to 67 (average 59). The results are compared with those from a control group of 20 healthy male volun-ters aged 32 to 58 (average 48).Table II shows the results obtained (mean ± SD) for the parameters found to be significantly different to those of the control group. An increase is seen in the levels of FPA, functional t-PA and PAI in the lung cancer group. In the case of the extensive -lung tumor patients, FPAfpa and t-PA levels are significantly higher than for the group of locally advanced neoplasmas.The plasma of lung cancer patients therefore shows fibrinolytic alterations and an increase in thromboplastin activity.
TUMOR CELLS INTERACTIONS WITH SUBENDOTHELIAL EXTRACELLULAR MATRIX IN A PERFUSION SYSTEM: ROLE OF PLATELETS
Authors: Ricetti M M , Samaden A , Fregoni V , Vigotti M , Piovella F , Ascari E 
Published: August 2018

It has been suggested that platelets may facilitate tumor metastasis by increasing tumour cell (TC) adhesion to vascular endothelium mainly through the formation of platelet/TC aggregates. In order to further investigate this we have utilized an in vitro model combining extracellular matrices (EM) from cultured vascular endothelial cells and two neoplastic clones from a mFS6 murine fibrosarcoma: one expressing high metastatic potency (M4) and one with low metastatic potential (M9). These two sublines express an in vitro platelet aggregating activity which has previously been characterized and which correlates with in vivo metastasizing capacity. To reproduce the in vivo flow conditions a flat perfusion chamber was used (*). Glass coverslips, carrying the EM were perfused for 10’ at a wall shear rate of 450 sec™1 with reconstituted heparinized human blood containing 3×10s/ml TC, with or without platelets. Coverage of the EM with adherent TC was evaluated by a morphometric method and expressed as percent TC coverage. M4 cells adhered to EM more than did M9 cells: 4.3% TC coverage for M4, versus 2.5% TC coverage for M9. In the presence of platelets, TC adherence was greatly increased, being 9.7% for M4 and 7.8% for M9. In the experiments performed in the presence of thrombocytes no platelet/TC thrombi were found onto the EM and no TC-induced platelet aggregation was detected in blood after perfusion. Our results confirm that platelets favour the occurrence of metastasis and suggest that other mechanisms than platelet/TC aggregates formation might be involved in this process.(*) K.S. Sakarlassen et al. J.Lab.Cl in.Med. 102:522, 1983
INTERACTION BETWEEN HEMOSTATIC COMPONENTS AND TUMOR CELLS
Authors: Esumi N , Todo S , Imashuku S 
Published: August 2018

Involvement of platelets and coagulation systems in the hematogenous metastasis of tumor cells has been suggested from in vivo and in vitro studies, however, there is still controversy about the exact role of hemostasis in metastasis. To date, at least three types of platelet aggregating mechanisms and three types of tumor cell procoagulants have been reported in different tumor cells.We investigated platelet aggregating activity (PAA), procoagulant activity (PCA) and the relationship between these two activities, using eight human neuroblastoma cell lines, three human leukemia cell lines and human mature lymphocytes. PCA in tumor cells was measured by the single stage recalcification time and the assay with chromogenic substrate S2222. PAA was determined turbidometrically with an aggregometer by adding cell suspensions of tumor cells to platelet rich plasma (PRP). The effects of protease inhibitors, enzymes and thrombin inhibitors on PAA and PCA were also studied.Neuroblastoma cell suspensions showed high PCAs which were reduced in Factor VII deficient human plasma, indicating a tissue factor-like activity. NCG line possessing the highest PCA also showed a high PAA, which was inhibited by pretreatment of cell suspensions with phospholipase A2 and abolished in the presence of heparin, hirudin or MD805 in the assay system. Human leukemia cell lines and mature lymphocytes had weak to moderate PCAs without showing PAA, but became active to express PAA after being removed of cell surface sialic acid by neuraminidase. These results suggest that in neuroblastoma, PCA closely linked with PAA may play a role in the hematogenous metastasis. In hemopoietic cells, PAA expressed when cell surface sialic acid is removed does not correlate with PCA, and sialic acid in these cells possibly prevents direct interaction with platelets in the hemostatic homeostasis.
SUBCUTANEOUS ENOXAPARINE (LOVENOXR) VERSUS PLACEBO FOR PREVENTING DEEP VEIN THROMBOSIS (DVT) AFTER TRANSURETHRAL PROSTATECTOMY (TUP)
Authors: LE GAGNEUX F , STEG A , LE GUILLOU M 
Published: August 2018

The aim of this study was mainly to evaluate the risk of bleeding, and the efficiency of Enoxaparine, a low-molecular-weight-heparin, in preventing DVT in patients undergoing TUP.89 patients (mean age : 67.5 years + 1.3), undergoing TUP, were included in a randomized, double blind study. Patients with a major risk of thromboembolism were excluded. 44 patients received one daily subcutaneous (SC) injection of 60 mg of Enoxaparine ; 45 patients received placebo. All the patients received the first injection 12 hours before operation.Red cell transfusions requirements were not significantly different between the two groups : 18 % of patients in the Enoxaparine group and 13 % of patients in the placebo group received red cell transfusions (p = 0.57). The amount of red cell units required was 3.3 units ± 0.9 in the Enoxaparine group and 2.5 U ± 0.8 in the placebo group (p = 0.51). The urethral catheters were removed on the 4th post operative day in each group.There was no significant difference in daily hemoglobin levels between the two groups.No DVT occurred : 125I fibrinogen scanning was negative in all patients but two : in these two patients (one in each group), DVT was not confirmed by a radiographic phlebography. No pulmonary embolism occurred.Enoxaparine, begun 12 hours before operation, however injected at high dose (60 mg/24 hrs), is safe in patients undergoing TUP. No significant bleeding complication occurred in the Enoxaparine group comparing with the placebo group. Red cell transfusions requirements were the same in both groups. There was no DVT in our patients.Enoxaparine (LOVENOXR) - PHARMUKA S.F.
PREVENTION OF DEEP VEIN THROMBOSIS (DVT) AFTER TOTAL HIP REPLACEMENT (THR) by ENOXAPARINE (LOVENOXR) : ONE DAILY INJECTION OF 40 MG VERSUS TWO DAILY INJECTIONS OF 20 MG
Authors: PLANES A , VOCHELLZ N , MANSAT C 
Published: August 2018

Venous thromboembolism is a common complication in patients undergoing THR. In a previous open study, Enoxaparine, a low-molecular-weight-heparin, in a dose of 40 mg/24 hrs by SC injection, had been shown to be efficient in preventing DVT in these patients. This treatment was not associated with an increased risk of bleeding. The present trial compares the efficiency and the risks of bleeding of two regimens : treatment A (2 daily subcutaneous (SC) injections of 20 mg of Enoxaparine) and treatment B (1 daily SC injection of 40 mg of Enoxaparine).118 patients, over 40 years, with a non traumatic hip disease, requiring THR, were included in a randomized, double blind trial. 59 patients received the treatment A. 59 patients received the treatment B. In both groups administration of 40 mg of Enoxaparine was begun 12 hours before operation. Patients were treated for 12-15 days, until bilateral ascending phlebography (BAP) had been completed.Lower limbs BAP were performed in 114 patients. The frequency of DVT is low and is not significantly different between the two regimens : a DVT was detected in 1 of 57 patients who received the treatment A and in 6 of 57 patients who received the treatment B (p = 0.11) . No pumonary embolism occurred in the 114 patients.There was no serious bleeding complication, and the two groups are not significantly different on this point. 3 patients in each group had an important hematoma of the thigh. None required a surgical treatment. Red cell transfusion requirements were 3.88 U ± 1.71 in the group A and 3.5 3 U ± 1.06 in the group B (p = 0.20). There was no significant difference in daily hemoglobin levels between the two groups.One daily injection of 40 mg of Enoxaparine was as effective as two daily SC injections of 20 mg of Enoxaparine in preventing DVT, in patients undergoins THR. The frequencies of bleeding complications were the same in each group.Enoxaparine (LOVENOXR) - PHARMUKA S.F.
A DOSE RANGING STUDY DESIGNED TO ASSESS THE SAFETY AND EFFICACY OF A LOW MOLECULAR WEIGHT HEPARIN FRAGMENT (FRAGMIN) AS PROPHYLAXIS AGAINST DEEP VEIN THROMBOSIS
Authors: Kakkar V V 
Published: August 2018

A preliminary study has reported that a single daily injection of 2500 and 5000 U of Fragmin was equally effective in preventing deep vein thrombosis1 (DVT). All the patients who developed DVT (4.9%) had undergone surgery for malignant disease. However, small numbers of patients were investigated and therefore detailed subject analysis was not possible. In the present study, 1000 patients scheduled to undergo elective major abdominal, urological or gynaecological surgery were investigated. They received one of three regimens; 5000 (Group I), 2500 (Group II) or 1500 (Group III) U of Fragmin daily as a single injection. The 125I-fibrinogen uptake test was used to detect DVT. Operative and postoperative blood loss, transfusion requirements, fall in postoperative haemoglobin and frequency of haematoma formation were recorded to assess the safety of three regimens. An analysis of variance was carried out using a computerized statistical package. Isotopic DVT was detected in 60 patients (6.7%). 11.1% of patients with malignant disease and 5.8% with benign disease developed DVT (p 0.01). Data were also analyzed in respect of age and there was a highly significant increase in the frequency of thromboembolic disease in patients over sixty years (10.1%) compared to 2.6% in the under 60 group (p 0.001). Significant differences were observed in the frequency of bleeding complications in the three groups and these were related not only to underlying disease process but also the type of surgery being performed. The detailed results will be presented and a safe and effective regimen for different groups of patients will be defined.1. Efficacy and Safety of Two Regimens of Low Molecular Weight Heparin Fragment (Fragmin) in Preventing Postoperative Venous Thrombolism. Kakkar W, Kakkar S, Sanderson RM, Peers CE. Haemostasis 16(Suppl.2) 1986, pp 19-24.
THE SAFETY AND EFFICACY OF A LOW MOLECULAR WEIGHT HEPARIN (FRAGMIN) IN THE PREVENTION OF DEEP VEIN THROMBOSIS IN MEDICAL PATIENTS: A RANDOMIZED DOUBLE-BLIND TRIAL
Authors: Poniewierski M , Barthels M , Poliwoda H 
Published: August 2018

The safety and efficacy of 2500 anti-Factor Xa U of a low molecular weight heparin (Kabi 2165, Fragmin) subcutaneously once a day, and 5000 IU of standard unfractionated Heparin (KabiVitrum, Stockholm) subcutaneously twice daily as thromboprophylaxis was compared in 200 medical patients in a randomized double blind trial. According to the risk of DVT the patients were stratified before randomization in a high and low risk group. The high risk group consisted of 100 patients mainly with malignant diseases and/or previous history of thromboembolism, the low risk group of 100 patients with mainly myocardial infarction and/or coronary heart disease. The prophylaxis was given for seven to ten days. In 192 consecutive patients the clinical status and thermographic screening for DVT (leg temperature profiles, DeVeTherm) were daily evaluated. In two cases of suspected DVT and one case of suspected PE, the following phlebography or pulmonary scintigraphy were found to be negative. In the high risk group, one patient treated with Fragmin having a central venous catheter developed on day 10 symptoms of an arm vein thrombosis. There were no bleeding complications observed in either of the two treatment groups. Two patients with trombocytopenia (25.000 and 22.000/pl) due to chemotherapy and underlying malignant disease were successfully treated with Fragmin without developing any bleeding complications. In eight patients during Fragmin prophylaxis invasive diagnostic methods as heart catheterization, gastroscopy, bronchoscopy or spinal puncture were performed without noticing any bleeding events. 2500 anti-Factor Xa U of Fragmin gave plasma levels by anti-Factor Xa assay (S-2222, Kabi) of mean 0,1 U/ml when blood was sampled three to four hours after the subcutaneus application. There was no accumulation during the treatment periode observed.This study suggests that 2500 anti-Factor Xa U of Fragmin once daily is as safe and effective as 5000 IU of standard heparin twice daily in these medical patients. Especially in patients who need prophylaxis for a long time eg. with malignant disease, the once daily injection is welcomed.
INTER-INDIVIDUAL PHARMACOKINETIC VARIATIONS AFTER INTRAVENOUS (IV) AND SUBCUTANEOUS (SC) INJECTION OF CY 216 IN HEALTHY SUBJECTS
Authors: Boneu B , Houin G , Rostin M , Montastructure J L , d’Azemar P , Bayrou B 
Published: August 2018

We investigated the pharmacokinetic parameters and their inter individual variations of a low molecular weight heparin (LMWH) derivative (CY 216, Fraxiparine R, Choay). In a cross-over study, 100 anti Xa IC u/kg were injected in 12 healthy volunteers, either by IV or SC route, at one week interval. The pharmacological effects were followed on 12 serial citrated samples for 24h: - anti factor Xa (AXa) activity (chromogenic assay calibrated against CY 216); - APTT and thrombin clotting time prolongation. The main pharmacokinetic parameters (elimination half-life (T|); clearance (cl); distribution volume (Vd); bioavailability F (SC/ IV)) were calculated from the anti Xa activity curves using con-, ventional methods. The results (mean, range) indicated below confirm some classical properties of CY 216: poor anticoagulant effect (APTT-TT), even after IV injection, longer half-life than . standard Heparin (SH), distribution volume similar to plasma volume, excellent bioavailability of the drug.We also emphasize important inter-individual variations between volunteers, as known for the pharmacological effects of SH in vitro and ex-vivo. From those results it could be assumed that, as for SH, close monitoring of treatment with LMWH would be suitable with higher dosages, after validation of the correlations between those biological tests and clinical results.* anti Xa IC u : anti factor X activated Institut Choay unit.