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Biomedical subjects

C R Prentice

Publications and source records attributed to C R Prentice.

At least 55 records · Page 3Linked to original sources
PubMed1988

Acute changes in blood glucose concentration do not promote thrombin generation or fibrin breakdown in type 1 diabetes.

To investigate the effect of blood glucose concentration on thrombin generation and fibrinolytic activity, six Type 1 patients had the blood glucose concentration maintained for 1 h at 5, 15, and 25 mmol l-1, and 8 patients underwent hypoglycaemia of 20 min duration after the blood glucose had been kept at 8 mmol l-1 for 1 h. During hyperglycaemia plasminogen activator activity rose from 214 (11-625) (median, range) to 478 (18-772) units (p less than 0.05) at a blood glucose of 5 mmol l-1 and to 511 (89-816) (p less than 0.05) and 535 (33-976) (p less than 0.05) units at a blood glucose of 15 and 25 mmol l-1, respectively. Cross-linked fibrin degradation products (FDP) were 45 and 53 micrograms l-1 at a blood glucose of 5 mmol l-1 and remained unchanged at higher glucose levels. Fibrinopeptide A was 1.3 (0.6-2.8) nmol l-1 at a blood glucose of 5 mmol l-1, and remained unchanged with hyperglycaemia, being 1.3 (0.9-1.3) nmol l-1 after 1h at 25 mmol l-1. During hypoglycaemia, plasminogen activator activity rose from 155 to 745 units (p less than 0.05) while both fibrinopeptide A and cross-linked FDP remained unchanged. The results indicate that acute fluctuations in blood glucose concentration do not lead to thrombin generation. Additionally, increased fibrinolytic activity measured in vitro is not associated with an increase in cross-linked FDP. This suggests that short-term hyper- and hypoglycaemia do not affect the end-products of the coagulation and fibrinolytic pathways.

Blood Glucose↗
PubMed1988

Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.

Coronary Angiography↗
PubMed1987

Hormonal control of haemostasis during hypoglycaemia in diabetes mellitus.

Factor VIII (FVIII) and plasminogen activator activity (PAA) rise during hypoglycaemia, and this might contribute to the vascular complications of diabetes. Similar changes in haemostasis accompany raised plasma levels of vasopressin (aVP) and adrenaline. To investigate the effects of these hormones on haemostasis during hypoglycaemia and the role of plasma insulin concentrations, eight insulin-dependent diabetic patients underwent controlled hypoglycaemia for 20 min and 13 diabetic patients were investigated during hyperinsulinaemia with blood glucose maintained at 8.0 mmol/l. During hypoglycaemia, insulin levels increased to median values of 114 mU/l, a VP rose from 0.5 to 4.4 (p less than 0.005) pg/ml and adrenaline from 0.4 to 4.4 nmol/l (p less than 0.005). FVIII coagulant activity (FVIII:C) rose from 0.75 to 1.09 IU/ml (p less than 0.01) and the ristocetin co-factor (FVIIIR:Co) and von Willebrand factor antigen (vWF:Ag) showed similar responses. PAA increased from 156 to 745 units (p less than 0.005). During hyperinsulinaemia, insulin rose following infusion from 24 to 52 and 118 mU/l, maintained for an hour at each level. Despite this, plasma aVP, FVIII:C, FVIIIR:Co, vWF:Ag and PAA remained unchanged. This study indicates that the marked changes in FVIII, vWF and PAA concentrations which accompany hypoglycaemia depend on low blood glucose and not raised plasma insulin. The response in probably mediated by increases in adrenaline and aVP, which are part of the physiological response to hypoglycaemia.

Adolescent↗
PubMed1987

Measurement of platelet loss in the blood compatibility assessment of biomaterials.

In the assessment of the in vitro blood compatibility of biomaterials, platelet loss is often attributed solely to platelet adhesion and consideration is not given to platelets lost in platelet aggregate formation. In order to distinguish between those platelets lost to adhesion and those lost to aggregate formation, the Wu and Hoak method for the quantification of circulating platelet aggregates in patients has been modified to establish a new test procedure. This procedure, which measures both platelet adhesion (PA) in the absence of platelets lost to aggregate formation and also the tendency of a material to induce aggregate formation, has been used to evaluate the influence of a range of polyamides and a hydrogel. The evaluation demonstrated the ability of polymers to induce readily platelet aggregates during in vitro blood-material contact. The sensitivity of the aggregate measurement was exemplified by the polyamides, where PA was similar for materials of different porosity but platelet aggregate formation increased significantly with porosity. The importance of considering platelets lost to aggregate formation was emphasized with the hydrogel, where PA was low.

Biocompatible Materials↗
PubMed1986

Intra-operative activation of coagulation--a stimulus to thrombosis mediated by vasopressin?

Vasopressin infusions in normal volunteers that produce concentrations in plasma comparable to those seen during stress, cause an increase in plasma factor VIII and shortening of the euglobulin clot lysis time (ECLT). We have investigated the relationship between endogenous vasopressin (aVP) release and haemostatic function in 7 patients undergoing major abdominal surgery. Blood samples were taken at nine intervals during the operative procedure. Plasma aVP levels peaked at median values of 51 pg/ml during bowel manipulation and remained elevated on the first post-operative day. Following, and in close temporal relationship with the rise in aVP there were increases in factor VIII coagulant activity, the ristocetin co-factor, von Willebrand antigen, plasminogen activator activity (10(6)/ECLT2) and fibrinopeptide A concentrations with shortening of the activated partial thromboplastin time. The relationship was similar to that seen following infusion of aVP in human volunteers. The results are consistent with the hypothesis that aVP is an important mediator of changes in haemostatic function which accompany stress and might contribute to the thrombotic risk associated with surgical operations.

Blood Coagulation↗
PubMed1986

Vasopressin and catecholamine secretion during apomorphine-induced nausea mediate acute changes in haemostatic function in man.

Seven male volunteers were given apomorphine (14-20 micrograms/kg) subcutaneously on a total of ten occasions. Nausea was experienced on six occasions and on four occasions there was no effect. Venous samples were taken before injection, at peak nausea and 20 min later for assay of factor VIII coagulant activity (FVIIIC), von Willebrand factor antigen (vWFAg), the ristocetin cofactor (FVIIIRiCof), euglobulin clot lysis time (ECLT), fibrinopeptide A (FPA), FPA generation time, activated partial thromboplastin time (APTT), vasopressin (aVP) and adrenaline. During nausea plasma aVP concentrations rose from median values of 0.4 pg/ml (at time 0) to 76 pg/ml at peak nausea and fell to 32 pg/ml 20 min later. Adrenaline rose from 0.36 to 0.91 nmol/l (P less than 0.05) before falling to 0.55 nmol/l. During nausea, FVIIIC rose from 100% to 143% (P less than 0.05) and to 214% (P less than 0.05) 20 min later. FVIIIRiCof and vWFAg showed similar changes. Plasminogen activator activity (10(6)/ECLT2) rose from 23 units at time 0 to 592 units during nausea and 1135 units (P less than 0.05) after 20 min. The APTT fell from 49 s to 44 s during the study, plasma FPA levels and the FPA generation time both remained unchanged. On the four occasions nausea was not experienced, there were no changes in vasopressin and catecholamine concentrations nor in haemostatic function. During the study, plasma aVP concentrations rose to levels previously shown to influence haemostatic function. This provides further support for the view that aVP has a secondary role as a mediator of acute changes in haemostasis, and during nausea contributes with adrenaline to an abrupt change in factor VIII and fibrinolytic activator activity.

Apomorphine↗
PubMed1985

Does hypernatraemia promote thrombosis?

Hypernatraemic states are associated with an increased risk of thrombosis. To examine the relative contributions of sodium and vasopressin, we infused hypertonic saline in 11 male volunteers and measured the effect on factor VIII (FVIII), euglobulin clot lysis time (ELT) and fibrinopeptide A (FPA) generation. Samples were taken pre-infusion, hourly during a 3h infusion of 450 ml 6M saline and one hour after the infusion had stopped. Mean plasma osmolality (SEM) rose from 287(0.7) to 302(10) mOsm after 3h (p less than 0.01). Plasma vasopressin concentrations rose from 1.0(0.3) to 4(0.94) pg/ml over 3 hr (p 0.01). Plasminogen activator activity (10(6)/ELT2) rose from 65(10) to 372(55) units (p less than 0.001). There was a highly significant correlation between plasma osmolality and plasminogen activator activity (r = 0.5 p less than 0.0001). FPA generation time shortened from 7.2(0.4) to 5.4(0.6) min after 2h and 5.3(0.6) after 4h (n = 6). Values for FPA after 4 min incubation steadily increased from 5.8(1.2) to 14.3(4.6) pmol/ml during the infusion but differences failed to achieve statistical significance. FVIIIC (1 stage) remained constant at 75(5.5%) during the infusion. There was a small and statistically insignificant increase in FVIII RiCof after 3h and FVIII RAg decreased slightly. The results suggest that hypernatraemia and increasing plasma aVP concentrations produce changes in haemostatic function consistent with a hypercoaguable state. The mechanisms for the effect are unclear. These changes in haemostatic function might contribute to the thrombo-embolic complications of conditions such as hyperosmolar coma in diabetes mellitus or severe heatstroke in which degrees of hypernatraemia occur.

Factor VIII↗
PubMed1985

A modification of the Wu and Hoak method for the determination of platelet aggregates and platelet adhesion.

The Wu and Hoak method for determining circulating platelet aggregates has poor reproducibility; problems have been reported with the composition of the buffer systems, haemolysis, the effects of blood collection technique and a divergence of the platelet aggregate ratio in blood for healthy donors from the theoretical value of 1. Our investigations suggest that the original technique is highly operator-dependent, especially the collection of blood and the method of counting platelets after centrifugation. We describe an improved modification of the Wu and Hoak technique; a new buffer system has been developed and the proportion of blood in the buffered EDTA and buffered EDTA-formalin solutions has been altered to obtain platelet rich plasma. The platelet aggregate ratio (PAR) by this modified method for healthy donors in two different studies was 0.97 +/- 0.02 and 0.98 +/- 0.01 respectively. Finally, the principle of Wu and Hoak was used to measure accurately platelet adhesion, without the role of platelet-platelet interactions (aggregation). Platelet adhesion and aggregation were then used to evaluate the thrombogenicity of various artificial surfaces, including silicone rubber and polytetrafluoroethylene (PTFE) vascular grafts.

Blood Specimen Collection↗
PubMed1985

Effects of oral stanozolol used in the prevention of postoperative deep vein thrombosis on fibrinolytic activity.

Plasminogen, fibrinogen, antithrombin III, euglobulin lysis time, tissue plasminogen activator (t-PA) and fast-acting t-PA inhibitor were measured in 21 patients receiving either stanozolol (10 mg orally given for 14 days preoperatively) or subcutaneous heparin, during a continuing comparative trial in the prevention of postoperative deep vein thrombosis. Stanozolol treatment resulted in significant (p less than 0.01) increases between the 14th and 1st preoperative days in the plasma concentrations of plasminogen (3.4 to 4.9 Cu/ml) and antithrombin III (107% to 132%); t-PA levels did not increase significantly (6.0 to 16.0 mU/ml; p greater than 0.1). There were significant (p less than 0.02) falls in fast-acting t-PA inhibitor (132% to 75%) and fibrinogen (2.4 to 1.8 g/l). Surgery reversed the changes in fibrinolytic activity seen preoperatively in the stanozolol-treated patients, and similar changes were seen in the heparin-treated group. In this dosage, stanozolol does not appear to prevent the fibrinolytic shutdown which occurs after elective major surgery.

Fibrinolysis↗
PubMed1985

Development of a radioimmunoassay for the measurement of prostacyclin metabolites in unextracted plasma.

Levels of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha) measured in normal subjects by radioimmunoassay show wide variation. In an attempt to develop a sensitive, specific and reproducible assay for the measurement of the circulating metabolites of prostacyclin (PGI2) we examined the different variables involved in radioimmunoassay such as choice of buffer; incubation time and temperature; amount of radioisotope tracer added and the separation method. The method described gives good reproducibility and shows good correlation with in vivo and in vitro doses of PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Effects of physiological concentrations of vasopressin on haemostatic function in man.

Plasma concentrations of vasopressin (aVP) attained under conditions of stress were simulated by infusing four volunteers with 0.25, 0.5, 1.0 and 2.0 pressor units of aVP over 1 h (units/h). Three subjects had all four infusions and one received only 1.0 unit/h. Blood samples were taken for assay of factor VIII coagulant activity (FVIIIC), factor VIII related antigen (FVIIIRAg), the ristocetin cofactor (FVIIIRiCof), euglobulin lysis time (ELT) and aVP concentrations before infusion (time 0) and every 20 min for 80 min. Fibrinopeptide A (FPA) generation time was measured at time 0, 60 and 80 min. At infusion rates of 0.25 unit/h median aVP levels peaked at 6.5 pg/ml and there was no change in FVIII or FPA generation time, and plasminogen activator activity (10(6)/ELT2) rose from 100 to 400 units. At 1.0 unit/h, aVP levels rose to 25.4 pg/ml, FVIIIC rose by 160% and activator activity from 87 to 360 units. At 2.0 units/h, aVP concentrations reached 83 pg/ml, there was an increase in all modalities of FVIII and activator activity rose from 251 to 452 units. FPA generation time shortened and circulating plasma levels of FPA were increased. There was a highly significant correlation between the percentage increases in all three components of FVIII and plasma aVP levels (FVIIIC: r = 0.87, P less than 0.0001; FVIIIRAg: r = 0.61, P less than 0.0001; FVIIIRiCof: r = 0.80, P less than 0.0001) and between the increase in plasminogen activator activity and aVP levels (r = 0.56, P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed1985

Acquired coagulation disorders.

An outline has been given of the major abnormalities of coagulation which can occur secondary to diseases in previously normal individuals. First, the disorders due to deficiency of the vitamin K-dependent clotting factors are described. Vitamin K deficiency can occur in the newborn, or at later stages in life when there is intestinal malabsorption. The malabsorption disorders, such as coeliac disease, together with major abdominal surgery or prolonged use of broad-spectrum antibiotics can give rise to vitamin K deficiency. Additionally, in obstructive jaundice the lack of secretion of bile salts into the upper intestine causes vitamin K malabsorption. The use of oral anticoagulants is associated with haemorrhage in a small proportion of patients. These patients usually have an excessively prolonged prothrombin time, due to overdosage with anticoagulants, but occasionally haemorrhage can occur from a localized bleeding site, such as a duodenal ulcer, in patients under good anticoagulant control. The large number of drugs which can interact with anticoagulants are listed, from which it can be seen that careful monitoring of all patients on oral anticoagulants must be carried out. The haemostatic defects associated with liver disease are then tabulated. In this situation abnormalities may be due to deficient synthesis of coagulation factors in hepatocellular failure, by failure of vitamin K absorption, and also by disseminated intravascular coagulation (DIC). DIC occurs in hepatocellular failure, because the liver cells are normally responsible for clearing activated products of the coagulation and fibrinolytic enzyme systems. The presence of clinical haemorrhage and haemostatic breakdown in hepatic disease usually indicates a serious prognosis, but appropriate replacement therapy is indicated in this situation. Disseminated intravascular coagulation embraces a large number of clinical haemorrhagic syndromes, where intravascular activation of the coagulation system takes place accompanied by compensatory fibrinolytic activity. DIC can be initiated by intravascular release of procoagulant substances, such as tissue thromboplastin, or by damage to vascular endothelium and platelets. The main clinical conditions associated with DIC comprise the severe infections and septicaemias, obstetric accidents, shock and trauma, neoplasia and snake-bite envenoming. In all instances, the pathophysiological disorder of haemostasis is managed by treating the underlying disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia, Hemolytic↗