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Biomedical subjects

C R Prentice

Publications and source records attributed to C R Prentice.

At least 19 recordsLinked to original sources

Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation.

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.

Adult

Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity.

The aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5-6.2) mmol/l to 3.6 (2.9-4.6) mmol/l; factor VII from 113 (92-145)% of normal to 99 (85-107)%; of fibrinogen from 3.5 (3-9.3) g/l to 2.8 (2.4-3.8) g/l; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11-30) IU/ml to 6.3 (5-10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100-204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease.

Adult

Effects of pimobendan (UDCG 115) on renal function in healthy volunteers.

A phase I, double-blind, single-dose, randomized, two-period crossover study was conducted to investigate the effects of pimobendan on renal function to assess whether renal events were a contra-indication to its administration. Results in eight healthy volunteers indicated no significant adverse events on renal plasma flow, glomerular filtration rate, or laboratory safety screens; side-effects were also found to be minimal. Further studies are indicated to assess whether, in the proposed treatment group, i.e. patients with heart failure (in whom compromised renal function is common), pimobendan similarly elicits no serious adverse renal effects.

Adult

Haemostatic responses and vasopressin release during colonoscopy in man.

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

Adult

Renal function and other factors in obstructive jaundice.

Renal function and other factors that possibly affect the outcome of operation were measured in 24 patients with obstructive jaundice and in 15 non-jaundiced controls. The preoperative features that were associated with a poor postoperative recovery from obstructive jaundice were a raised serum fibrinogen/fibrin degradation product concentration, infection, hypoalbuminaemia and a low glomerular filtration rate. Preoperative serum fibrinogen/fibrin degradation product concentrations were raised in 4 of the 6 jaundiced patients who died after surgery but in none of the controls, in whom there was no mortality. In the jaundiced patients there was a greater incidence of postoperative renal impairment than in the controls. All patients were given mannitol during operation. Further mannitol was required after surgery in 13 of the 24 jaundiced patients in order to maintain urine flow rate despite adequate intravenous fluids being given. In contrast, only 1 of the 15 control patients required post operative mannitol. It is emphasized that repeated doses of mannitol can lead to a profound natriuresis and adequate intravenous saline should be given.

Cholestasis

Mesterolone: thrombosis during treatment, and a study of its prothrombotic effects.

1. We describe a patient who developed deep vein thrombosis after commencing treatment with the synthetic androgen, mesterolone (Pro-Viron). 2. To investigate the potential thrombogenic action of this drug, a 21 day course of mesterolone (100 mg/day) was given to nine healthy male volunteers. 3. No significant change after treatment occurred in any of the blood tests performed (clotting times, Factor VIII coagulant activity, Factor VIII related antigen, antithrombin III activity, fibrinogen, fibrinogen-fibrin degradation products, plasminogen, euglobulin lysis time, urokinase sensitivity, platelet count, haematocrit, whole blood viscosity and plasma viscosity). 4. We conclude that in a conventional dose taken for 3 weeks mesterolone does not produce a consistent measurable prothrombotic state, nor does it enhance fibrinolysis.

Adult

The effect of an injectable progestogen contraceptive on blood coagulation and fibrinolysis.

In 26 women receiving either medroxyprogesterone acetate (Depo-Provera) injections or combined oestrogen-progestogen pills for contraception, tests of coagulation and fibrinolysis were performed before treatment, and after 8, 16 and 24 weeks of therapy. In the medroxyprogesterone group no significant changes were induced in fibrinogen, the vitamin K-dependent factors, or antithrombin III. Plasminogen levels fell during therapy, and were significantly lower than pre-treatment values after 16 and 24 weeks. By contrast, the 13 women receiving oral contraceptives showed raised levels of fibrinogen and plasminogen after 8 weeks of treatment, and of factors VII and X after 24 weeks. These data suggest that medroxyprogesterone acetate injections induce fewer changes in the blood coagulation system than oral contraceptives.

Adult

Subcutaneous ancrod therapy in peripheral arterial disease: improvement in blood viscosity and nutritional blood flow.

Nine patients with extensive peripheral arterial disease were treated with subcutaneous injections of ancrod (Arvin) for 10 to 21 days. Reduction in plasma fibrinogen was associated with a sustained reduction in plasma and blood viscosity, and a sustained increase in nutritional skin blood flow, measured by a Xenon-133 clearance technique (P less than 0.001). These findings may be relevant to the therapeutic effect of ancrod in ischemic rest pain.

Adult

A study of the effect of sulphinpyrazone ('Anturan') on blood viscosity.

A double-blind, placebo-controlled crossover study of the effect of sulphinpyrazone on blood viscosity and its determinants (haematocrit, plasma fibrinogen and plasma viscosity) was carried out in 7 healthy male volunteers. Apart from a transient rise in fibrinogen (p less than 0.05) after 3 days of sulphinpyrazone treatment, no significant change in viscosity factors was seen over a 14-day period.

Adult

Subcutaneous ancrod in prevention of deep-vein thrombosis after operation for fractured neck of femur.

In a randomised double-blind controlled trial 53 patients received 5 daily subcutaneous injections of ancrod ('Arvin') after operation for fractured neck of femur, and 52 patients received saline fractured neck of femur, and 52 patients received saline injections. Deep-vein thrombosis (D.V.T.) was detected by bilateral ascending venography or necropsy 6--16 days after surgery. The frequency of D.V.T. and bilateral D.V.T. was significantly lower in the ancrod group (P less than 0.01). The frequency of major D.V.T. (thrombi in veins proximal to the calf, or calf-vein thrombi more than 3 cm long) was also significantly lower in the ancrod group (P less than 0.001). No complications of ancrod prophylaxis occurred. Ancrod reduced plasma-fibrinogen, and hence plasma and blood viscosity, during the first week after surgery; preoperative levels of fibrinogen and viscosity were not associated with post-operative D.V.T. Subcutaneous ancrod is a simple and effective alternative to oral anticoagulants for the reduction of the frequency of D.V.T. after operation for hip fracture, and merits assessment in other high-risk groups of patients.

Adult

Subcutaneous ancrod after operation for fractured hip--a dose-ranging and feasibility study.

We have conducted a dose-ranging and feasibility study of daily subcutaneous injections of ancrod (Arvin) as a potential antithrombotic method in 28 patients following operation for fractured neck of femur. Sustained, predictable fibrinogen depletion during the first post-operative week was induced by four different regimes. A total dose of 10 units/kg weight, given in divided doses starting on the day of operation, is suggested as a possible antithrombotic regime. Ancrod treatment produced a rise in fibrinogen/fibrin degradation products, prolongation of the thrombin clotting time, and a fall in plasminogen, plasma fibrinogen and corrected blood viscosity were observed in 14 control patients. Plasma fibrinogen was correlated with plasma viscosity and corrected blood viscosity. No adverse effects of treatment occurred. Subcutaneous ancrod appears to be a simple, safe, and feasible potential antithrombotic method, and merits trials of efficacy in the prevention of post-operative thromboembolism.

Adult