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Biomedical subjects

C V Prowse

Publications and source records attributed to C V Prowse.

At least 73 records · Page 4Linked to original sources
PubMed1984

Metabolism of sodium pentosan polysulphate in man--catabolism of iodinated derivatives.

An iodinated derivative of the heparin analogue SP54 has been prepared and used in conjunction with unlabelled SP54 to study the catabolism and organ distribution of this potential antithrombotic agent in healthy human volunteers. As observed previously with 125I-heparin, we found that the 125I-SP54 was rapidly cleared from the circulation, returning later in a desulphated form. Organ distribution studies with 123I-SP54 suggested that the liver and spleen were major sites of desulphation. Gel filtration and Polybrene binding showed the presence of sulphated macromolecular SP54 and desulphated macromolecular and depolymerised SP54 in post-injection urines. No depolymerised material was present in plasma suggesting depolymerisation occurs in the kidney.

Adult↗
PubMed1984

A hypothalamic-pituitary system that stimulates the release of plasminogen activator in the rat.

We have studied the possible role of the hypothalamic-pituitary system in the control of the release of plasminogen activator (PA) into peripheral blood of male rats. Plasminogen activator was measured by euglobulin lysis time. Desamino-D- arginine vasopressin (dDAVP) and adrenaline injected i.v. induced an increase in plasma PA as did electrical stimulation of the median eminence (ME), but dDAVP had no effect on plasma PA in hypophysectomized rats. The PA response to ME stimulation was similar in Brattleboro rats (deficient in vasopressin) and adrenalectomized Wistar rats compared with intact Wistar rats, but was abolished by section of the pituitary stalk and was negligible in hypophysectomized rats. The 41-residue corticotropin releasing factor (CRF) had no effect on PA release. Saline extracts of anterior pituitary gland from both normal Wistar and Brattleboro rats produced a dose-dependent increase in plasma PA when injected into normal Wistar rats. The activity of pituitary tissue was abolished by boiling, but not by di-isopropyl fluorophosphate which inactivates PA itself. Thus the anterior pituitary gland of the rat contains a heat-labile factor which stimulates the release of PA from peripheral stores into the circulation. This pituitary factor is released by a hypothalamic factor that is neither vasopressin nor CRF.

Animals↗
PubMed1984

A comparative study using immunological and biological assay of the haemostatic responses to DDAVP infusion venous occlusion and exercise in normal men.

In a group of six normal male volunteers, infusion of DDAVP, venous occlusion and exercise were shown to increase plasma levels of factor VIII and plasminogen activator, activity and antigen, to different extents and at differing rates. Any mechanisms suggested to explain release of these proteins by various stimuli should account for such differences. All three stimuli could also increase plasma levels of prostacyclin metabolites, although this was only significant for high doses of DDAVP. Other potential endothelial markers, such as fibronectin and thrombospondin, showed no specific increase after any of the stimuli.

Arginine Vasopressin↗
PubMed1984

Platelet and coagulation factors in proliferative diabetic retinopathy.

Plasma beta-thromboglobulin, platelet factor 4, fibrinogen, fibrinopeptide A, antithrombin III, factor VIII related antigen, alpha 2-macroglobulin, platelet count, and total glycosylated haemoglobin were measured in three well matched groups of subjects: non-diabetic controls, diabetics without retinopathy, and diabetics with proliferative retinopathy. beta-thromboglobulin and platelet factor 4 concentrations were significantly higher in the diabetics with retinopathy than in the controls and platelet factor 4 was also increased in the diabetics without retinopathy compared with controls. Fibrinogen concentration was raised in diabetics without retinopathy compared with controls, diabetics with retinopathy compared with controls, and diabetics with retinopathy compared with those without. Fibrinopeptide A concentration did not differ significantly between groups. Antithrombin III levels were increased in diabetics with retinopathy compared with controls, and in diabetics with retinopathy compared with those without. Factor VIII related antigen values were higher in both the diabetic groups when compared with the controls. Fibrinopeptide A concentration correlated with both beta-thromboglobulin and platelet factor 4 in each of the three groups. Haemostatic abnormalities in diabetes have been shown, although a hypercoagulable state has not been confirmed. These changes in platelet and coagulation function may be secondary to the development of microvascular disease and their role in the pathogenesis of retinopathy remains uncertain.

Adult↗
PubMed1983

A radioimmunoassay for thrombospondin, used in a comparative study of thrombospondin, beta-thromboglobulin and platelet factor 4 in healthy volunteers.

A radioimmunoassay was developed for the platelet alpha-granule protein thrombospondin; concentrations of thrombospondin as low as 3 ng ml-1 could be measured. There was no interference from other components of human biological fluids and no crossreactivity with beta-thromboglobulin (beta-TG) or platelet factor 4 (PF4). Plasma samples were stable when stored at -20 degrees C. Normal human plasma contained 105.0 +/- 31.0 ng thrombospondin ml-1 compared with beta-TG concentrations of 37.2 +/- 10.9 ng ml-1 and PF4 concentrations of 14.7 +/- 10.1 ng ml-1 when samples were carefully taken into a platelet inhibitor cocktail and processed at 0-4 degrees C. Release of thrombospondin during clotting of blood occurred at the same time as that of beta-TG and PF4 and resulted in a serum concentration of 17.5 +/- 5.5 micrograms ml-1. Assay of whole blood gave a platelet thrombospondin content of 89.1 +/- 28.3 ng/10(6) platelets. The concentration in normal urine fluctuated widely from 3 to 22.5 ng ml-1, and was unrelated to urine flow. The half-life of thrombospondin in vivo was about 9 h, much longer than that of either beta-TG or PF4. Unlike PF4, it was not released into the blood following an intravenous heparin injection. Bovine, ovine, canine and porcine sera contained thrombospondin which crossreacted immunologically with the human molecule; these species would be suitable animal models for the study of thrombospondin and its value as a platelet release marker.

Adult↗
PubMed1982

The in vivo release of human platelet factor 4 by heparin.

Intravenous and subcutaneous injection of heparin or the heparin analogue SSHA into normal volunteers induced release of platelet factor 4 (PF4) but not beta-thromboglobulin (beta-TG). At low heparin doses the amount of PF4 released was related to the plasma heparin concentration achieved. The rise in plasma PF4 was coincident with, and appeared to be a response to, the increase in plasma heparin concentration rather than to the absolute heparin level. After the primary response, the system became refractory to further challenge by the same heparin dose; the full initial magnitude of the response was not regained until 144 h. after heparin was first injected. The maximum amount of PF4 released corresponded to only about 5% of that potentially available from platelets. Moreover, heparin did not stimulate PF4 release from whole blood in vitro. We have demonstrated the presence of PF4 on the vascular endothelium, and suggest that this is the immediate source of the PF4 released by heparin, though it is probably initially derived from platelets. The effect of such binding on the antithrombotic potential of the endothelial surface is discussed.

Animals↗
PubMed1982

Proteolysis of fibrinogen in healthy volunteers following major and minor vivo plasminogen activation.

Changes in immunoreactive fibrinopeptide A, fragment B beta 1-42 and fragment E were followed after major and minor in vivo plasminogen activation, after infusion of streptokinase and acylated streptokinase-plasminogen complex respectively, in healthy male volunteers. Major activation resulted in a dramatic rise in all three peptides, fragment E persisting in the circulation longest. Fragment B beta 1-42 was also markedly increased after minor systemic plasminogen activation despite apparently adequate levels of immediate antiplasmin.

Anistreplase↗
PubMed1982

A comparison of acylated streptokinase-plasminogen complex and streptokinase in healthy volunteers.

The in vivo effects on the fibrinolytic and coagulation system of infusion acylated streptokinase-plasminogen complex (BRL 26921; 5, 7 and 12 mg) or streptokinase (250,000 u) were determined in healthy male volunteers. While this dose of streptokinase resulted in depletion of plasminogen and antiplasmin, and in some cases of fibrinogen and coagulation factors V and VIII, the equivalent 7 mg dose of BRL 26921 had little effect on these parameters. 12 mg BRL 26921 had some systemic effects on the fibrinolytic system. For initial clinical studies a dose of 10 mg BRL 26021 would seem appropriate. Both drugs induced an anamnestic rise in streptokinase antibody, whereas no change in liver function tests were observed. A delayed mild febrile reaction was observed in some subjects following infusion of streptokinase or BRL 26921. Clinical, laboratory, and subjective monitoring revealed no other adverse effects with either drug.

Adult↗
PubMed1982

Activated prothrombin complex concentrates: approaches to their preparation.

Locally produced prothrombin complex concentrate was activated by different methods and the resultant inhibitor bypassing activity compared with commercially produced activated concentrates using an assay based on the shortening of the clotting time of haemophilic plasma containing inhibitor to factor VIII. Analytical chromatography suggested that for most of these products the inhibitor bypassing activity could be explained in terms of classical activated coagulation factors. In addition, a preparation of Bridge Anticoagulant Neutralising Activity was examined. The results indicate this product merits in vivo investigation as a possible treatment for inhibitor patients.

Blood Coagulation Factors↗
PubMed1981

Coagulation abnormalities following intensive plasma exchange on the cell separator. II. Effects on factors I, II, V, VII, VIII, IX, X and antithrombin III.

The effects of intensive plasma exchange on the circulating levels of coagulation factors I, II, V, VII, VIII, IX, X and antithrombin III were determined. During courses of daily exchange marked cumulative reductions of coagulation factors may occur, particularly in the case of factors I, II and X, although usually remaining above the levels considered adequate for haemostasis. The extent of cumulative reduction and subsequent recovery differed for patients with different diseases. While antithrombin III levels were reduced during plasma exchange the results suggest that this may be partly due to consumption as well as physical removal. The very low incidence of haemorrhagic sequelae and absence of thrombotic events following plasma exchange at this Centre is explained by the maintenance of adequate levels of coagulation factors and of antithrombin III even during courses of daily plasma exchange.

Antithrombin III↗
PubMed1981

A clinical trial on the early detection and correction of haemostatic defects in selected high-risk neonates.

Low birth weight infants, preterm infants with respiratory distress syndrome and mature infants with asphyxia were screened for coagulation abnormalities as soon as possible after birth. Those with abnormal haemostasis were assigned to control or treatment groups and, in the latter case, were given prothrombin complex concentrate, cryoprecipitate or platelet concentrate as appropriate. This treatment was largely successful in correcting haemostatic defects but did not result in any change in mortality. There was no evidence of adverse or beneficial side-effects of treatment.

Asphyxia Neonatorum↗
PubMed1981

The use of factor IX concentrates in man: a 9-year experience of Scottish concentrates in the South-East of Scotland.

During the last 9 years, two factor IX concentrates produced in Scotland, PPSB and DEFIX, have been used for the treatment of haemophilia B and acquired coagulation disorders, including those due to liver disease, coumarin therapy, neonatal immaturity and post-operative bleeding. During the period of study 112 batches of DEFIX and 40 batches of PPSB were used in the Edinburgh and South-East Scotland Region. Data were analysed from 575 non-haemophilic patients, receiving 968 treatment episodes, as well as 24 haemophiliacs. Serial coagulation studies and analysis of retrospective data showed that both concentrates corrected the coagulation deficiencies in all the above patient groups; in no case was there any evidence of intravascular coagulation resulting from concentrate infusion.

Blood Coagulation Disorders↗
PubMed1981

Changes in factor VIII complex activities during the production of a clinical intermediate purity factor VIII concentrate.

Samples taken at various stages of preparation of intermediate purity factor VIII concentrate were assayed for factor VIII coagulant activity (VIII:C), factor VIII coagulant antigen (VIIIC:Ag) and factor VIII related antigen (VIIIR:Ag). The antigen results were used to assess mechanical loss during fractionation as these markers are relatively stable. In contrast VIII:C is sensitive to both mechanical and inactivation losses. The major loss of factor VIII occurred during the cryoprecipitation and extraction step and was due to both mechanical loss and inactivation. Losses before and after this step were largely due to inactivation of the factor VIII. Assay of VIIIR:Ag in concentrates presented problems and a modified technique is suggested.

Antigens↗
PubMed1980

A comparison of the in vitro and in vivo thrombogenic activity of factor IX concentrates using stasis (Wessler) and non-stasis rabbit models.

The thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vivo tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo. These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Animals↗
PubMed1980

In vitro thrombogenicity tests of factor IX concentrates. I. A survey of available assays.

Various factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

Blood Coagulation Tests↗
PubMed1980

In vivo characteristics of thaw siphon cryoprecipitate compared to other factor VIII preparations.

5 severe haemophiliacs were infused with cryoprecipitate prepared by the continuous thaw-siphon technique, with cryoprecipitate prepared by overnight thawing and with intermediate-purity factor VIII concentrate. All 3 preparations gave a similar mean half-life for coagulant factor VIII of approximately 10 hours. The immediate recovery of this activity was similar for the 2 cryoprecipitates, but higher for the purified concentrate.

Adult↗