bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal Pulmonary Embolism In Total HIP Replacement
Authors: Fredin H O , Nillius A S
Published: July 2018

A retrospective study of fatal pulmonary embolism (FPE) was carried out in 1498 hips during 1968 - 1979. Dextran 70 was given as thromboprophylaxis, no anaphylactic reactions were registered. Sixteen patients died within 3 months, autopsy was made in fourteen cases. Nine patients died from FPE within 3 months, eight patients were autopsied.

Comparing this group with a surviving group chosen by random from the whole material we found that acute attacks of pleuritic chest pain was more common (p < 0.001) as well as previous operations for orthopedic and gynecological reasons (p < 0.05) in the group of FPE. No difference could be found between the groups concerning blood loss, amount of transfusion, sex, operated side, type of prosthesis and body weight.

Conclusions: 1. FPE was the most common cause of death within 3 months after THR.

2. The incidence of FPE was 0.6% in 1498 patients treated with Dextran 70 prophylaxis.

3. Acute attacks of pleuritic chest pain in the postoperative period is an important symptom which should be followed by a lungscan to rule out pulmonary embolism.

4. Only chest radiogram is not sufficient for the evaluation of acute pleuritic chest pain after THR.

5. Heparin therapy for a short period did not prevent FPE in cases with scintigraphic diagnosis of pulmonary embolism.
Sulfinpyrazone And Prevention Of Postoperative Deep Venous Thrombosis(DVT)
Authors: Arapakis G , Trovas A , Orphanoudakis G , Vassilikos P
Published: July 2018

Though the antithrombotic properties of sulfinpyrazone (SP) in arterial thrombosis have been documented, its value in phlebothrombosis remains uncertain. In this randomized double-blind trial, the effect of SP (500mg I.M. twice daily for the first 10 postoperative days) on postoperative DVT was compared with a placebo control group. 96 (65 male and 31 female) patients 41 to 83 years of age undergoing major surgical operations were included in the trial. The composition of the two groups (treated and placebo) were homogenious regarding age, sex and type of operation (0,30<p<0,50). The incidence of DVT was estimated clinically and isotopically by the 125I-labelled figrinogen test.

No clinical phlebothrombosis was observed in either group but DVT was detected isotopically in 4 (8,3%) out of 48 in the placebo and in 7 (14,5%) of the 48 in the SP group. Analysis by the x2 showed no statistical significance in the prevalence of postoperative DVT between the two groups (x2<x20,30/1). These results suggest that SP has no place in the prevention of postoperative DVT.
Thrombosis Prophylaxis Using External Compression
Authors: Caprini J A , Chucker J , Zuckerman L , Vagher J P , Franck C A , Mitchell J
Published: July 2018

Seventy-seven surgical patients, high risk for D.V.T., were randomized and stratified using 17 risk factors; 39 patients were assigned long leg elastic hose (TED) and 38 patients long leg sequential pneumatic compression devices (SCD). The TED or SCD were placed on the patient immediately following the anesthesia and continued for at least 72 hours postoperatively. Doppler, impedance, and 125I-fibrinogen scans were done daily and venography performed if these screening tests indicated thrombosis. Daily coagulation and fibrinolytic studies were done on all patients. Abdominal surgical patients were 65% of the group, 13% were orthopedic, 10% neurosurgical, and 10% genitourinary. Screening tests were positive in 7 (9.1%) patients, but only 3 (3.9%) of the seven had positive venograms. 5.3% of TED patients (2/39) developed nonfatal DVT. One TED patient developed nonfatal pulmonary embolus (2.5%). One SCD patient (2.6%) had both nonfatal DVT and pulmonary embolus. Statistically significant increase in fibrinolytic activity was only seen in the orthopedic-neurologic SCD group. An additional 88 patients not randomized for this protocol were studied. These patients had fibrinogen scans and contrast venography if the scans were positive. 60 (68%) had TED hose; 15 (17%) were controls, and 13 (14.7%) had SCD. In all, 60% were orthopedic patients; 25% were abdominal surgery, and 15% were miscellaneous. 8 TED patients (13.3%) developed calf vein thrombosis of which 2 had clots extending proximally and one death occurred 3 days postoperatively from myocardial infarction. One SCD patient developed nonfatal pulmonary emboli (7.6%) while 4/15 of control patients (26.6%) developed calf vein thrombosis. These studies suggest that SCD and TED are both effective thrombosis prophylaxis methods compared to the control group. Subgroup differences in fibrinolytic activity may reflect pathologic problems, length of immobilization, method of leg compression, etc.
Erythrocyte Adhesion To Endothelial Cells And Glycosylated Haemoglobin
Authors: Paton R C , Galacteros F , Wautier M P , Bluekit Y , Wautier J L
Published: July 2018

We have observed increased erythrocyte adhesion to cultured endothelial cells in diabetes mellitus (see Wautier et al.). This study was designed to determine if glycosylated haemoglobin is involved in this abnormal RBC-endothelial interaction. Erythrocytes from 29 diabetic subjects were examined. Adhesion was measured using 51Cr-labelled erythrocytes and calculated by counting the radioactivity remaining after 5 washes. The percentage of haemoglobin A1 (HbA1) was measured by a standard microcolumn technique. Mean HbA1 concentration was 11.4%, with a range of 6.8 to 17% (upper limit of normal 7.5%). Adhesion, expressed as an adherence ratio, did not correlate with the level of HbA1 (r 0.23, n.s.). To investigate if a sub-population of erythrocytes with an elevated HbA1c adheres more strongly to endothelial cells, we have measured the concentration of HbA1c in RBC from successive washes. The erythrocytes from 5 diabetics were studied, with a range of concentrations of HbA1c between 9.8-12.6% (measured by a column technique). In each experiment, the RBC from a diabetic were incubated on 8 identical endothelial cultures. The cultures were then rinsed and the non-adhering erythrocytes from each of the 5 washes were pooled and the HbA1c was measured. HbA1c (mean±SEM) in the 5 washes varieacbetween 10.94±0.49 and 11.26±0.49%.

These results indicate that increased adhesiveness of erythrocytes from diabetics is not related to the concentration of glycosylated haemoglobin.
Morphology Of Vital Avian Thrombocyoid Cells
Authors: Janzarik G
Published: July 2018

The morphologic criteria of vital avian throm- bocytoid cells are not well established. In the present study the different forms of chicken and duck thrombocytoid cells have been analyzed by phase and interference contrast microscopy and compared with those of erythrocytes, erythrocyte ghosts, granulocytes, monocytes, and lymphoid cells.

Since the nucleated thrombocytoid cells do not differ in size from the other white blood cells, they can easily be confused with them and even with the nucleated erythrocyte ghosts which also are capable of adhesion and aggregation but do not spread. According to previous investigations using membrane immunofluorescence tests, thrombocytoid cells may be closely related or identical with B lymphocytes (Janzarik et al. Developmental and Comparative Immunology 1980, 4,123). However, thrombocytoid cells are the only cells with platelet-like spreading and strong adhesion to collagen fibrils. In fresh blood specimens they are spherical and cannot be differentiated morphologically from lymphoid cells. After aging in vitro, suspended thrombocytoid cells elongate to spindle forms.
Some Observations On Platelet Amino Acid Transport Systems
Authors: Yardimci U T , Özbilen A , Ulutin O N
Published: July 2018

We have studied the transport systems for amino acids in platelets. Na+/K+ dependent active transport systems were found to be responsible for the transport of amino acids through the platelet membrane (Km’s being at uM ranges). We have also isolated the binding proteins for amino acids from platelet membranes as the carriers involved in these active transport systems by cold osmotic shock procedure. Each amino acid besides being transported by a specific active transport system may be subject to transport by group amino acid transport systems.

Group amino acid transport systems are classified by countertransport experiments as follows:
Neutral amino acid group transport systems:
IA: glycine, alanine, serine, threonine
IB: valine, leucine, isoleucine, serine,threonine
IC: cysteine, methionine, proline
Basic amino acid group transport systems:
lie: lysine
IIB: histidine, arginine
Acidic amino acid group transport systems:
III A: Aspartic acid, glutamic acid Aromatic amino acid group transport systems:
IVC: Phenylalanine,tyrosine, histidine, proline.
Protein Synthesis By Platelets In Vitro
Authors: Shaw T , Chesterman C N
Published: July 2018

The ability of platelets to synthese proteins in vitro, in particular the a-granule secretory proteins, has been investigated following platelet isolation by a method which causes minimal leakage of granule contents.

Platelets were isolated by three cycles of Percoll density gradient centrifugation from citrated blood taken from normal donors. Platelet suspensions prepared by this method represent over 90% of the starting population, show negligible (<.002%) leukocyte and plasma protein contamination, and remain capable of aggregation and secretion.

When 1 ml. aliquots of platelet suspension containing ≃108 platelets were incubated at 37°C in a humid 5% CO2/ 95% air atmosphere with lµCi 3H leucine or 3H protein hydrolysate, incorporation of label into TCA precipi table material proceeded linearly over a 3 hour period, plateauing after 4 hours. Inhibition of label incorporation was produced by addition of cold amino acids, cycloheximide, puromycin, chloramphenicol, ethidium bromide, fluoride or homologous platelet free plasma which had been exhaustively dialysed to remove free amino acids, but not by addition of albumen, γ globulin, actinomycin D or vincristine sulphate.

A differential release of label paralleling granule secretion could not be demonstrated when, after incubation, thrombin was added at concentrations known to produce a graded dose/response in terms of granule secretion without cell lysis. To date, no peaks of radioactivity have been found to correspond with elution patterns of granule proteins when release produces have been separated by affinity column chromatography following labelling.

The limited capacity of platelets for protein synthesis may be controlled by (a) plasma factor(s), and, at least in normal individuals, does not appear to include the ability to synthesise secretory proteins.
The Effecet Of Aspirin On The Activity Of Platelet Density Subpopulations As Measured By Electrophoretic Mobility
Authors: LeBeau R J , Menna J A , Guntuer R C
Published: July 2018

Whole populations of platelets were harvested from male subjects by centrifugation at 60g. Density subpopulations in the ranges: 1.040≤p1≤1.058, 1.058 ≤p2≤1.068, and 1.068 ≤p3≤1.080 were obtained using the Stractan method of Corash. These correspond approximately to the “light,” “medium,” and “heavy” subpopulations of Karpatkin. Electrophoretic mobilities (EB) of normal platelets and those following the subjects’ ingestion of aspirin where measured using a Zeiss Cytophero- meter. It is shown that there is a highly significant difference in EB between the three subpopulations of normal platelets and that the EB of the heavy group is significantly more affected by aspirin than that of the medium and light groups.
Affinity Chromatography Used To Identify Asa-Binding Proteins From Human Plasma
Authors: Kirchmaier C M , Fink G , Bender N , Breddin K
Published: July 2018

By the formerly used analytical methods it was not possible to show the binding of Acetylsalicylicacid (ASA) to proteins, if the acetyl-group of the ASA was not transferred to the protein. Using affinity chromatography it was possible to demonstrate the simultaneous non covalent binding of several proteins of a human plasma fraction to the immobilized ligand ASA.

To this purpose we synthesized a new photoreactive ASA-analogue N3-ASA, which was coupled to SEPHAROSE 4B, using 3,3’- /mino-bis-propylamine as a spacer.

The isolated proteins were identified by SDS-poly- acrylamide gel-electrophoresis and by immunoelectrophoresis. After eluation of the column albumin and two proteins with a molecular weight of about 200 000 Daltons bound to ASA were found.

Affinity chromatography using the N3-ASA analogue may be a new useful tool to investigate the non covalent binding of ASA to proteins and to reveal unknown ASA- effects not mediated by the transfer of the acetyl- group
Ticlopidin In The Prevention Of Platelet Hyperaggregation In Surgery
Authors: Scrobohaci M L , Petrilắ T , Mihắitắ D , Alexapdrescu M , Pop I , POpa D
Published: July 2018

The effects of ticlopidin on platelet function was estimated in two groups of patients: group I: 9 patients with thrombocytosis (6 chronic granulocytic leukaemia patients, 3 idiopathic thrombocytopenic purpura patients); group II: 18 patients undergoing extracorporeal circulation (ECC)-(4 aorto-coronary bypass patients, 9 valvular patients and 5 congenital heart patients). Platelet function was assessed by the following tests: platelet aggregation (Born ’ s technique) with ADP and collagen; index of aggregated platelets (Wu and Hoak’s technique). The treatment with ticlopidin was administrated: in group
I (24-48h), in the postoperative period, when platelets were ≃500,000/mm3; in group II (24-48h), for the preoperative period (750 mg. daily).

The index of aggregated platelets normalized in group I - from 0.2 to 0.8 and in group II - from 0.4 to 0.8. The extent of platelet aggregation decreased in group I - from 80% to 20% and in Group II - from 50% to 20% at the beginning of anaesthesia before ECC.

We did not observe any haemorrhagic accident in the postoperative period in either group.
Pharmacology Of 12-Deoxyphorbol Phenyl Acetate (12-DOPP) Induced Human Platelet Aggregation
Authors: Westwick J , Williamson E M , Evans F J , Kakkor V V
Published: July 2018

12-DOPP (0.1 to 3.6µM) induced human platelet aggregation which was dependent upon the presence of divalent cations, intracellular level of C-AMP and an intact microtubular system in common with other aggregating agents. However, the small amount of platelet secretion and thromboxane (Tx) B2 synthesis did not contribute to 12-DOPP induced platelet aggregation as neither the Tx/endoperoxide antagonists pinane A2 (0.001-0.004mM) and trimethoquinone (0.01-0.1mM), the Tx synthesis inhibitors clotrimazole (0.1 to 0.8mM) and 9, 11, aza-prosta-5-13 dienoic acid (0.002-0.1) nor the cyclo-oxygenase inhibitor indomethacin (0.03-0.1mM) inhibited 12-DOPP induced aggregation. Furthermore the free radical scavengers aminopyrine (0.2-2.0mM), thioanisole (0.2-2.0mM) and butylated hydroxy toluene (0.07-1.4mM); the lipoxygenase inhibitor phenidone (0.5mM) and the leucotriene B and C antagonist FPL55712 (0.005-0.06mM) failed to modify 12-DOPP induced aggregation.

However compounds which are thought to act as phospholipase inhibitors bromophenacyl bromide (0.3mM), mepracrine (0.20mM) and propanolol (0.2mM) were found to be effective inhibitors of 12-DOPP induced aggregation as well as the so- called calmodulin antagonists imipramine (0.12mM), desmethy- 1imipramine (0.033mM), promethazine (0.1mM) and trifluoperazine (0.35mM).

The aggregation induced by 12-DOPP involves a direct effect upon platelets followed by the release of unknown substances probably phospholipids, which induce further aggregation of platelets.
Measurement Of Platelet Nucleotides By Reverse-Phase HPLC, And The Demonstration Of Acquired Storage Pool Defect In D.I.C
Authors: Porter N R , Brown P R , Malia R G , Preston F E
Published: July 2018

The most common methods for analysis of platelet adenine nucleotides have been either firefly-luciferase or enzyme based spectrophotometric assay. However HPLC provides ah alternative with advantages of direct, rapid and efficient analysis. Although this has usually been achieved by the use of ion exchange columns, this study relates to the development of a rapid 10 minute assay using reverse phase partition. Platelet preparations were extracted with perchloric acid, neutralised and subjected to a sample ‘clean up’step prior to injection. The selected manning conditions were isocratic elution using 0.15M pH5.45 NH4H2PO4 as solvent and a 4 minute linear gradient change in flow rate from 4 to 6 mls/min. at ambient temperature. Analyses were initially performed on yBondapak C18 columns of conventional type but the running conditions described relate to the use of radial compression types of this column. Sample peaks were identified by comparison with known standard retention times. The following normal range was established ATP 5.82 ± 1.14 n moles/108 plats. ADP 4.14 ± 1.45. AMP 0.28 ± 0.14 and ATP/ADP ratio 1.43 ± 0.48. ‘Within man’ precision showed that the coefficient of variation for ATP was 2.55%, ADP 3.26%, AMP 4.64%, whilst ‘between run’ precision for ATP was 9.03% and 11.98% for ADP. The value of nucleotide analysis was demonstrated in a group of five patients with DIC. Four patients had impaired platelet aggregation responses to ADP and collagen. Nucleotide analysis revealed significant reduction of intraplatelet ADP and ATP and increased ATP/ADP ratios. This confirms previous suggestions that acquired storage pool defects occur in DIC. In addition the low ATP levels indicate that in DIC there is also a reduction in metabolically active nucleotides.
Indium Labeled Platelet Kinetics In Ascitic Cirrhosis
Authors: Reiffers J , Couzigou P , Vuillemin L , Amouretti M , Beraud C , Ducassou D
Published: July 2018

Using Indium-oxine as platelet label, we performed platelet kinetic studies in 30 patients with ascitic cirrhosis. Spleen size was also assessed. All results were compared to that found in 10 controls

Seven patients had platelet kinetics not different from controls. Five of them were thrombopenie, and presented probably a platelet production insufficiency. Eighteen patients had a shortened platelet survival (less than 7.5 days). These patients were thrombocytopenic and presented a platelet destruction. The major site of destruction was splenic in ten out of these 18 patients. Only five patients had a normal platelet lifespan and an increased splenic pooling. No correlation was found between the following parameters: platelet count, platelet survival, splenic uptake of the radioactivity, spleen size.

It is concluded that in patients with liver cirrhosis and portal hypertension:
1) Hypersplenism (normal platelet survival and high splenic pooling) is a rare cause of thrombopenia.
2) Thrombopenia is probably due to several mechanisms which are associated in a same patient and which are independent of the spleen size.
Platelet Phagocytosis As A Model For Platelet Adhesion
Authors: Absolom D R , Zingg W , Neumann A W , van Oss C J
Published: July 2018

It has been suggested that platelet phagocytosis might be a useful model to provide insight into platelet adhesion to polymer substrates commonly employed in biocompatibility studies. To test this supposition the present study of platelet engulfment of four strains of bacteria (opsonized as well as non-opsonized) under well defined in vitro physical conditions was undertaken. In physiologic conditions, platelet adhesion is maximum on the more hydrophilic polymers and minimum on the more hydrophobic surfaces; bacterial engulfment under the same conditions follows an identical pattern in that the more hydrophilic bacteria are more readily engulfed. The experimental data further suggest that, unlike phagocytosis by neutrophils platelet interaction with bacteria is non-specific in that it does not appear to be antibody receptor modulated. Opsonization of the bacteria does however play an important role in that it serves to increase the hydrophobicity of the bacteria thereby influencing the degree of bacterial engulfment. A striking correlation between the extent of bacterial engulfment and the Helmholtz Free Energy of Engulfment exists. Platelet adhesion to polymer substrates and platelet engulfment of bacteria appear to follow the same thermodynamic model.
Retention Of Platelets In A Protein A-Sepharose Column As A Measure Of Platelet Associated IgG
Authors: Chesterman C N , McVeigh D J
Published: July 2018

Employing the biological property of staphylococcal protein A to bind human IgG a test system has been devised to detect platelet associated IgG (PAIg) by quantitating platelet retention in an agarose column with immobilised protein A.

Platelets were washed free of plasma and resuspended in Tyrode’s buffer with EDTA and 0.1% BSA. Platelet counts were performed on the suspension prior to and following passage through a miniature protein A column and the percentage of platelets retained calculated. An indirect test for serum platelet antibody utilised washed normal platelets following their incubation in patient serum.

Less than 30% normal platelets or normal platelets incubated in normal serum were retained in the affinity column. Similarly in four samples from patients with thrombocytopenia of nonimmune origin there was less than 15% retention in the column. Platelets from two of five patients with probable ITP (all treated with corticosteroids) showed 85% retention in the column. The remaining patients fell within the normal range. The sera from three patients with proven platelet antibody using other techniques produced 65-80% retention in an indirect test. Four other sera from possible ITP patients (with comparatively high platelet counts) showed less than 30% retention. Specificity for PAIg was suggested by inhibition of retention from 80% to less than 30% following pretreatment of the colurrai with purified IgG or normal serum.

The optimum conditions for the technique are being studied and its specificity and sensitivity ascertained in patients with thrombocytopenia of various kinds. If these preliminary results are extended, such a simple technique may prove of diagnostic value.
Differences In The Appearance Of Immunoprecipitate 16 (GP IIb/Gp IIIa) By Crossed Immunoelectrophoresis Of Triton Solubilized Platelet Proteins Depending On The Solubilization Conditions
Authors: Hagen I , Korsmo R , Bjerrum O J , Gogstad G , Solum N O
Published: July 2018

Crossed immunoelectrophoresis (CIE) of Triton solubilized platelet proteins has demonstrated that the major immunoprecipitate (16) represents GP IIb and GP IIIa. CIE of proteins solubilized from isolated membranes has often showed patterns with reduced area or absence of immunoprecipitate 16 concomitant with the appearance of new arcs.

The aim of this study was to establish conditions to control this phenomenon. By CIE of proteins solubilized from platelet membranes isolated in the presence of EDTA, the area of immunoprecipitate 16 was reduced, and two new arcs, one at the cathodic side (16a) and one at a similar position (16b) as immunoprecipitate 16 appeared. In contrast, CIE of extracts from corresponding membranes which had been washed once in an EDTA-free medium revealed one major 16 peak. Despite the major differences between these patterns, SDS PAGE of these extracts showed no differences in the glycoprotein patterns. The anodic leg of immunoprecipi- tate 16a fused with 16, and a specific antibody obtained by immunozation with immunoprecipitate 16 also reacted with 16a. Partial or total disappearance of immunoprecipitate 16 was also seen after CIE of proteins solubilized from whole platelets in the presence of EDTA, whereas leupeptin had no such effect. The different patterns may reflect biochemical alterations related to platelet activation.
On The Separation Of Thromboplastic And Platelet Stimulation Activity And On The Phospholipid Content Of Various Tissue Extracts
Authors: Kirchmaier C M , Bender N , Breddin K
Published: July 2018

Homogenisates of different human and animal tissue induce rapid and reversible platelet changes, enhance platelet aggregation and induce platelet retention. These findings led to the hypothesis, that paravascular and other tissues contain a “Hemostasis Activating Factor” HAF, which is locally liberated at the site of a tissue injury. Enzymatic digestion of crude tissue extracts by phospholipase D and Neuraminidase destroyed the platelet stimulating activity. Separation by thin layer chromatography using chloroform-methanol (70:30) as eluant resulted in five zones. Staining by different media showed phospholipid, protein and glycoprotein compounds. Testing different lipids and phospholipids we found that Lyso- dimethylcephaline and Sphyngosine induced morphologic platelet changes in high concentrations (10-3 g%) while other compounds were almost inactive. The tissue extracts contained a very weak thromboplastic, but some partial thromboplastic activity. Using Amicon CF25 cones the platelet stimulating activity was found in the ultrafiltrate which contained no thromboplastic or partial thromboplastic activity. The unfiltrated higher molecular weight supernatant showed a strong partial thromboplastic activity, but only a slight platelet stimulating activity. The partial thromboplastic activity in tissue extracts from different organs (subcutaneous tissue, lung, muscle, vessels, brain) showed a large variation and did not correlate with platelet stimulating effects. So for instance brain extracts showed the well known partial thromboplastic activity while they contained only a weak platelet stimulating activity.
Activation Of Platelets In Chronic Glomerulonephritis (CGN) And Nephrotic Syndrome (NS)
Authors: Yamazaki H , Motomiya T , Sakakibara C , Ariga S , Ida T , Kuriyama R , Kuriyama R , Chida Y , Takeuchi J , Tomura S
Published: July 2018

Platelet count, volume, aggregation, adenine nucleotide contents, plasma β-thromboglobulin (β-TG) , plasma platelet factor 4 (PF-4) and urineβ-TG were measured in 31 patients with CGN, 20 patients with NS and 51 healthy controls. Platelet counts were higher and volumes were smaller in NS than in controls significantly. Platelet aggregation induced by ADP, adrenaline and collagen was significantly higher in the patients than in controls and it markedly increased in the cases of progressive glomerular lesions. Plasma levels of β-TGwere significantly elevated in the patients (65.8± 7.5(SE) ng/ml) compared with controls (22.2±1.6 ng/ml) and NS showed markedly elevated plasma β-TG levels (124.3±28.6 ng/ml). Plasma levels of PF-4 were also significantly higher in the patients (28.6±3.6 ng/ml) than in controls (13.2±1.1 ng/ml). There was a significant inverse correlation between plasmaβ-TG and creatinine clearance (r=-0.47, P<0.01).
Urine β-TG excretion was higher in patients with decreased renal function than in those with normal renal function. Plasma β-TG remarkably decreased in 3 of 4 patients with markedly increased β-TG levels when they were given antiplatelet drugs. Platelet ATP contents were 6.98±0.24 in the patients and 8.06±0.42 μmoles/1011platelets in controls. There was a significant difference (P<0.05). Platelet ADP contents were 3.08±0.15 in the patients and 3.27±0.19 in controls.

The results suggest that platelet aggregation and release reaction increased in patients with CGN and NS. However the decrease in adenine nucleotides in platelets was more marked in ATP than in ADP content. There may be an abnormal metabolism of adenine nucleotides in platelets related to the energy metabolism in addition to a decrease in storage pool in such diseases. Also it is suggested that activated platelets may be an important factor in the genesis of thrombotic tendency in NS.
Hyperaggregability Of Platelets In Cancer, Especially In Reference To Genesis Of DIC
Authors: Yamazaki H , Yahara Y , Motomiya T , Tanoue K , Isohisa I , Jung S M , Onozawa Y
Published: July 2018

To clarify the role of platelets in the genesis of DIC in cancer, platelets of cancer patients with and without DIC were examined. Patients studied were 29 cases with cancer in stomach, 17 in lung, 7 in pancreas, 6 in liver (hepatoma), 6 in throat, nose and jaw, 2 in the gall bladder and bilary duct, 2 in uterus and 1 each in the small bowel, rectum and prostate, and 1 each with osteosarcoma, mesothelioma and chorionepithelioma. All patients were in stage 3 or 4. 105 healthy controls were also studied. They were evaluated on a scale of coagulation abnormalities, one point was given for each of the following criteria full-filled, and the score (0 to 4) was used. 1. Platelet count<150xl03Anl. 2. Prothrombin time prolonged more than 1 sec over control and/or activated partial thromboplastin time prolonged more than 10 sec over control. 3. Fibrinogen<250 mg/dl (mean fibrinogen value of the cancer patients minus 1 SD). 4. FDP>20 µg/ml. The patients were distributed with 27 % for score 0, 38 % for 1, 20 % for 2, 7 % for 3 and 8 % for 4. Degrees of abnormality in groups with scores of 3 and 4 were significant when compared to scores 0 and 1, but score 2 was not clearly distinguishable. Platelet mode volume in score 4 was smaller than the other groups. Platelet aggregation by adrenaline and ADP decreased in score 3 and 4, while it increased significantly in score 0 and 1 respectively (P<0.01 -0.05). The mean value of plasma β-TG in the cancer patients as a whole (44±24 ng/ml) was significantly higher than that of control (22±13 ng/ml)(P<0.01). PF4 showed the same tendency. During the time course of the disease, hyperaggrega- bility of platelets associated with increases in β-TG and PF4 was observed before an appearance of DIC syndrome in several cases. The results suggest the existence of hyperfunction of platelets in cancer patients and the possibility of triggering mechanism of such activated platelets in the genesis of DIC in cancer.
Effects Of The Thromboxane Synthetase Inhibitor Uk37243 On Monolayer Adhesion Of Rabbit Platelets
Authors: Davies J A , Menys V C
Published: July 2018

Vasoconstriction and platelet aggregation in response to thromboxane A2 are thought to be important in thrombo- genesis. We assessed the effects of inhibition of thromboxane synthesis using UK37248 on platelet monolayer adhesion. This was quantitated as uptake of washed, Na 51Cr-label led platelets onto collagen-coated glass or damaged rabbit aorta, using a perfusion device. UK37248 did not inhibit adhesion to collagen-coated glass. At luM final concentration and in the presence of washed rabbit red cells, UK372A8 caused a significant (p< 0.001) reduction in platelet adhesion to damaged rabbit aorta from 122,000 ± 17,000 to 65,600 ×A,500 platelets per mm2 (mean × SEM). In the absence of red cells platelet adhesion was much less but addition of 1μM UK37248 similarly reduced adhesion to about 50% of control value (p<0.05). Dose-ranging experiments at concentrations from 0.3 to 10μM showed maximal inhibition of adhesion (52%) to damaged aorta at 1.0μM concentration. Failure to inhibit adhesion to a nonvascular surface suggested that PGI2 might be involved in the reaction. We are investigating the possibility that UK37248 inhibits platelet adhesion to damaged aorta due to synthesis of PG12 by vascular cells from endoperoxides accumulating in platelets.
Inhibition Of Platelet Adhesion To Glass By Human β-Lipoprotein
Authors: Sharma N C , Mohammad S F , Chuang H Y K , Mason R G
Published: July 2018

Platelets, by virtue of their seemingly innate adhesiveness to many nonbiologic surfaces, appear to play an important role in blood-material interactions that may lead to the dysfunction of extracorporeal or implanted devices that contact blood. A number of attempts have been made in the past to minimize the adhesion of platelets to artificial surfaces in order to improve their compatibility with blood by use either of pharmacologic agents or plasma protein preparations. We describe here inhibition of platelet adhesion to glass by β-lipoprotein. β-lipoprotein was purified from human serum preincubated at 37°C for 16 hr, by normal and sodium bromide density ultracentrifugations at 320,000 × g for 24 hr at 4°C. The β-lipoprotein preparations were homogeneous when tested with specific rabbit antihuman β-lipoprotein antiserum in immunoelectrophoresis and antigen-antibody crossed immunoelectrophoresis. In electrophoresis in 1% agarose gels β-lipoprotein migrated as a single band. The band reacted with both the protein revealing stain Coomassie brilliant Blue R-250 and the Oil Red o stain for lipids. The effects of purified β-lipoprotein on the adhesiveness of gel filtered human platelets to glass were studied by the centrifugation method. β-lipoprotein at a concentration of 23 mg/ml inhibited platelet adhesion by about 61% when compared with values obtained when platelets were suspended in phosphate buffered saline alone. Delipid- ation of β-lipoprotein resulted in complete loss of its platelet adhesion inhibitory activity mainly due to denaturation and insolubilization of the protein moiety. These observations suggest the possibility of improving the compatibility of artificial surfaces that contact blood either by coating the foreign surfaces with β-lipoprotein or by adding concentrated preparations of the protein to blood.
The Effects Of Prostacyclin (PGI2) On Intravascular Platelet Aggregation
Authors: Duncan G G , Mallarkey G , Smith G M
Published: July 2018

Intravascular aggregation can be measured by counting the number of circulating platelets before and after the injection of aggregation agents. The Technicon Autocounter was modified to count platelets continuously and connected via a double cannula in a carotid artery to an anaesthetised animal.

Adenosine diphosphate (ADP) and collagen gave dose- dependent falls in the circulating platelet count when injected into rats, guinea pigs and rabbits. This enabled aggregation to be accurately quantitated in vivo.

The infusion of PGI2 (0.25-1 ug/kg/min) in anaesthetised rats and rabbits produced a dose-dependent inhibition of the fall in platelet count produced by ADP and collagen. The formation of PGI2 can be inhibited in vitro by 15- hydroperoxyarachidonic acid (15HPAA). When 20 ug/kg/min of 15HPAA was infused into rats, aggregation produced by collagen was significantly increased suggesting that PGI2 is continuously formed by the rat vascular endothelium. This observation was confirmed by infusing 6-keto PGF1α antiserum. This antibody also prevented the inhibitory activity of PGI2 on collagen-induced aggregation. The study of continuous platelet counting in guinea pigs has been hampered by the occurrence of thrombocytopenia in certain animals. When 2 ug/kg/min of PGI2 was infused for 10 mins, a rise in the circulating platelet count to a steady plateau 4-5 × 105 platelets occurred

These experiments have shown that PGI2 will prevent aggregation by ADP and collagen and will reverse spontaneous thrombocytopenia and that PGI2 is continuously released from the vessels of anaesthetised rats.
A Study Of The Mechanisms Involved In Collagen-Induced Intravascular Platelet Aggregation
Authors: Smith G M , Mallarkey G
Published: July 2018

Intravascular platelet aggregation can be monitored by measuring the fall in the number of circulating platelets after the injection of an aggregating agent. The Technicon Auto-counter was modified to count platelets continuously. Rats were anaesthetised and the trachea and jugular vein were cannulated. A double cannula was inserted into a carotid artery.

Collagen gave consistent and dose-dependent falls in platelet count. Infusion of trisodium citrate gave a dose- dependent inhibition of collagen-induced aggregation with 2 mg/kg/min producing 100% inhibition. Indomethacin 1-8 mg/kg and aspirin 10-l60 mg/kg produced up to 60% inhibition of collagen-induced aggregation giving a biphasic dose-response curve. Sulphinpyrazone 20-160 mg/kg and piroxicam 1-8 mg/kg gave dose-dependent inhibitions of aggregation. None of the cyclo-oxygenase inhibitors studied or sulphinpyrazone completely inhibited collagen- induced aggregation. Attempts to produce 100% inhibition by infusing adenosine or low doses of citrate with indomethacin were unsuccessful. High doses of collagen were more resistant to cyclo-oxygenase inhibitors than low doses of collagen.

This study has shown that trisodium citrate will completely inhibit collagen-induced aggregation and that both high and low doses of collagen produce aggregation in the rat that is partially mediated by products of arachidonic acid metabolism. The biphase nature of the dose-response curves obtained with indomethacin and aspirin suggests that the higher doses are inhibiting the cyclooxygenase in the walls of blood vessels as well as in platelets thus reducing the endogenous release of prostacyclin. The nature of the arachidonic acid- independent pathway has yet to be demonstrated.
Platelet Uptake On Bioprosthetic Heart Valves
Authors: Oyama C , Klein S , Magilligan D J
Published: July 2018

Single and aggregated platelets have been a consistent finding on the surface of 28 degenerated porcine bioprosthetic heart valves. Both the degenerated valves as well as unimplanted commercially available valves exhibit loss of endocardium with bare collagen fibers on scanning electron microscopy. The role of platelet adherence to the collagen fibers of these glutaraldehyde treated bioprostheses in causing degeneration is an unanswered question. Platelet adherence to porcine (P) valve (Type III collagen) and bovine (B) pericardium (Type I collagen) was measured in the glutaraldehyde treated bioprosthesis and in the fresh state with saline (F, S) and with plasma (F, P). Single cusps or similar samples of pericardium were rotated at 200 RPM for 10 min in a concentration of human platelets tagged with 51Cr. The tissue was trimmed to standard size, counted in a gamma counter and adherence calculated as platelets (pits)/mm2.

Our experimental observations did not show a difference in platelet adherence between porcine or bovine tissue either G-treated or F. The G-treated valves showed significantly less (p=<.01) adherence than the F tissue. Although G- treated bioprostheses have collagen fibers exposed to circulating blood, platelet collagen reaction probably does not play a primary role in degeneration of the bioprosthetic heart valve.
Vascular Changes During Resolution Of Pulmonary Arterial Hypertension
Authors: Rawlings Clarence A , Keith James C , Schaub Robert G
Published: July 2018

Pulmonary hypertension associated with myointimal proliferation is produced by low grade, sustained damage to the arterial surfaces by Dirofilaria immitis (DI) infection in dogs. This study correlated changes during and after infection in pulmonary vascular hemodynamics, arteriograms, and morphology {scanning electron microscopy (SEM) and light microscopy (LM)}. Seven beagles were infected with 50 infective DI larvae. Twelve months after infection, mild pulmonary hypertension {mean pulmonary arterial pressure (MPAP) during normoxia was 26.4 mmHg versus 16.0 pre-infection, during isoproterenol infusion was 37.6 vs. 14.3 pre-infection and reduction of pulmonary vascular resistance was 31.1% versus 47.2% pre-infection} was present. Angiograms at this time revealed dilation and tortuosities of the main and intralobar pulmonary arteries. SEM revealed large villus proliferations, disoriented cell axis, and pore formation. The villi projected (LM) into the vessel lumen and consisted of intimai thickening with multiplying smooth muscle cells and collagen.

Seven months after treatment to eliminate the DI as a cause of the arterial trauma, pulmonary hypertension was resolved (MPAP of 19.8 during normoxia, 17.7 during isoproterenol infusion, and reduction of pulmonary vascular resistance of 45.2%). The arteriographie changes of dilation, aneurysms, and tortuosities were decreased, especially in the main and lobar arteries. LM revealed that larger arteries, which had greater arteriographie resolution, had relatively more elastic tissue and that the intralobar arteries had more collagen. SEM revealed that the villus proliferations were markedly reduced in numbers and sizes. This study characterized a reduction of hypertension as related to resolution of the muscular hypertrophy of arteries and related arteriographie changes to the type of connective tissue being produced by smooth muscle cells in the arterial wal.
Treatment Of Impaired Rheologic Conditions With Pentoxifylline (PO) In Patients With Cerebrovascular Disease (CVD)
Authors: Lechner H , Ott E
Published: July 2018

Investigations have been performed in 55 patients (25 femals, 30 males) with a mean age of 61 years presenting focal neurological deficit due to acute or subacute CVD. Impairment of hemorheologic conditions has been diagnosed in more than one third of the patients using blood viscosity, hematocrits, fibrinogen and spontaneous as well as induced platelet aggregation (PA) as indicators. Blood viscosity has been determined by a cone - plate viscometer at four different shear rates and PA has been investigated using a modification of BORN’S method.

Impaired hemorheologic conditions have been treated with Pentoxifylline (PO) during a period of 3 weeks administering 4,2 - 17,1 mg/kg body weight intravenously and/or by mouth. Thus, blood viscosity decreased significantly with a maximum decrease at low shear rates (11 sec -1) while hematocrits did not change. Likewise, mean fibrinogen levels decreased significantly during PO medication. Epinephrine as well as ADP induced PA have been succesfully inhibited by PO. However, drug induced changes of rheologic parameters were more pronounced when 17 mg/kg body weight were administered.

It was concluded that PO is an effective drug for treatment of impaired rheologic conditions in patients with CVD.
Platelet Aggregability In Healthy And Ischemic Heart Disease (IHD) Donors: A Unique Aggregometry Parameter Practically Independent Of Platelet Count Or Drugs Such As Acetylsaly- Cilic Acid
Authors: Frojmovic M M , Milton J , Yung W , Brandwejn J , Wong T , Burgess J , Rose C
Published: July 2018

We report on a uniquely useful parameter of platelet aggregation derived from aggregometry tracings for adenosine diphosphate (ADP)-induced aggregation in citrated platelet- rich plasma, pH 7.4, 37°C., for 13 healthy and 13 IHD donors (6 post-myocardial infarct (2-16 days), and 1 acute coronary insufficiency (7 days) (group I) and 6 angiographically characterized coronary artery disease (group II). A double reciprocal (L-B) plot of [ADP] (1-100 µM) against the velocity of light transmission increase associated with platelet aggregation obtained for the initial velocity (V) or for the maximal velocity (V*) was usually linear only at high ADP (≥ 5 µM), from which a Vmax value could be extrapolated. We then derived [ADP]l/2:- [ADP] yielding V=l/2 Vmax, from a Hill-type plot ((log (V/Vmax-V) vs log [ADP]). Only [ADP] 1/2 values derived from V* allowed a highly significant (P≥ 0.001) distinction to be made between healthy and IHD donors (2.4 ± 0.4 µM (n=13) vs 1.3 ± 0.3 µM (n=7, group 7, group I; n=4/6, group II)). Other parameters such as extent of primary or maximal aggregation did not distinguish IHD from normal donors, and could not be normalized for varying platelet counts. 2/6 donors in group II (coronary artery occlusions) and 4 donors with normal angiographs had “normal” [ADP] 1/2 = 2.5 ± 0.4 µM. One recall of a 7 day postmyocardial infarct donor after 7 weeks still exhibited “abnormal” [ADP] 1/2 = 1.0 vs 1.4 µM. This new parameter appears independent of normal hematocrit-citrate/platelet count variations, or of drug type including aspirin, and promises to be useful for classification of diseases according to platelet aggregabilit.
Alteration In Platelet Factor 3 Activity In Plasma In Association With Cigarette Smoking
Authors: Chao F C , Kenney D M , Tullis J L , Alper C A , Silbert J E
Published: July 2018

Changes in blood coagulation and platelet functions in vivo in healthy smoking and non-smoking individuals of different age groups were studied. Blood samples were obtained on four different occasions (6 months apart during 1978-1980) from each of the 21 smokers and 42 non-smokers (age range 35-79), and analyzed. Statistically significant changes (p < 0.03) associated with cigarette smoking are:
1) increases in platelet count and fibrinogen in plasma;
2) elevation in a platelet procoagulant, platelet factor-3 (PF-3) activity in platelet-poor plasma (PPP); 3) increases in serum levels of α1-antitrypsin, orosomucoid, haptoglobin and properdin factor B; and 4) shortening of the lag period of collagen-induced platelet aggregation. Filtration through Millipore filters removed membrane vesicles which are enriched with PF-3 activity from the PPP. The difference in PF-3 activity in filtered plasma between the smoking and non-smoking groups were no longer statistically significant. The results are consistent with the interpretation that enhanced PF-3 activity in plasma occurs in association with cigarette smoking and results from the liberation into plasma of platelet membranes enriched in PF-3 activity.
The Anatomical Distribution Of Adpase Activity In The Rabbit Aorta
Authors: Emms Helen , Lewis G P
Published: July 2018

Human and rabbit aorta have been shown to be capable of degrading ADP and a role for this ADPase enzyme has been suggested in the regulation of arterial thrombosis.

The anatomical distribution of ADPase activity in the rabbit aorta has been investigated. The whole aorta, removed from exsanguinated rabbits, was divided into 6 sections and intact cells prepared by digestion with a mixture of enzymes. The cells were suspended in 0.25M sucrose and incubated for up to 40 minutes at 37°C with 14C- ADP (480µM-30µM) . ADP remaining in the incubation mixture was assayed by platelet aggregation and radiochromatography (which also enabled identification of the ADP metabolites).

All 6 sections of aorta were capable of degrading ADP and its removal was time-dependent. The aortic arch and upper thoracic aorta, however, metabolised ADP only slowly and the rate of metabolism increased from the upper to the lower aorta. The lower abdominal sections removed ADP at the fastest rat.

The major metabolite produced from ADP by the aortic arch and upper thoracic aorta was AMP. Middle and lower thoracic sections produced only AMP at 480µM ADP, whilst AMP,inosine and adenosine were produced at lower substrate concentrations. However, upper and lower abdominal sections produced AMP, inosine and adenosine at all concentrations of ADP.

Atherosclerosis in rabbits has been reported to be more severe in the aortic arch and upper thoracic aorta than in the abdominal aorta. These results therefore suggest a connection between ADPase activity and the incidence of atherosclerosis. In the aortic arch and upper thoracic aorta, where ADPase activity is low, and adenosine, an inhibitor of aggregation, is not formed, there is a high incidence of the disease and conversely in the abdominal regions where ADPase activity is high and adenosine is formed the incidence of the disease is low.
Does Uremia Promote Atherogenesis?
Authors: Horsch A , Heuck C C , Hofmann W , Kühne W , Bisson M , Ritz E
Published: July 2018

The development of experimental atherosclerosis was studied in subtotally nephrectomized rats which were subjected to preimmunisation with horseradish peroxidase and subsequent feeding with atherogenic diet. Both in sham operated pairfed control animals and in uremic animals, the atherogenic diet caused hyperlipemia which was more pronounced in uremic than in control animals (control animals: triglycerides 1.11 ± 0.04 mmol/1; cholesterol 5.82 ± 0.21 mmol/1; uremia: triglycerides 1.33 ± 0.06; cholesterol l0.9 ± 0.31). An increase of cholesterol was seen both in the VLDL and in the LDL fractions. Despite more pronounced hyperlipemia, lipid concentration in the aortic wall was not increased nor were more marked histological abnormalities encountered in the aorta of uremic animals.

The results suggest that despite hyperlipemia short term experimental renal insufficiency does not promote atherogenesis.