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Biomedical subjects

C R Prentice

Publications and source records attributed to C R Prentice.

At least 91 records · Page 5Linked to original sources

Bronchial carcinoma in von Willebrand's disease. Successful removal after hemostasis with lyophilized cryoprecipitate.

A man with severe von Willebrand's disease who had hemoptysis was followed-up for 2 1/2 years for continued hemoptysis and was discovered to have a bronchial carcinoma. Under close hematological surveillance, an uncomplicated pneumonectomy was performed, using a new factor VIII product--freeze-dried cryoprecipitate. This case illustrates that hemoptysis in von Willebrand's disease cannot always be attributed to the disease itself: that continued hemoptysis requires regular bronchoscopy and that major surgery can be performed in von Willebrand's disease with effective correction of the coagulation defect using freeze-dried cryoprecipitate.

Bronchial Neoplasms↗

Effects of growth hormone, glucose and insulin on the factor VIII complex.

The relationship of growth hormone (GH) to the factor VIII complex (VIIIC, VIIIRAg and VIIIRRCo) was investigated. No correlation between basal levels of GH and factor VIII assays was found in 23 subjects. No significant change in factor VIII assays was observed after GH suppression by oral glucose or bromocriptine. After insulin-induced hypoglycaemic all three factor VIII assays rose and fell in parallel with GH. However, after exercise the rise in VIIIC and VIIIRAg preceded the rise in GH; and no changes in factor VIII assays were observed after administration of thyrotrophin releasing hormone (TRH) (releasing endogenous GH) or exogenous GH. These findings do not support a role for GH in the regulation of plasma levels of VIIIC, VIIIRAg or VIIIRRCo.

Antigens↗

The effect of intramuscular stanozolol on fibrinolysis and blood lipids.

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p less than 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p less than 0.01) and remained elevated for three weeks. HDL cholesterol fell (p less than 0.01) and both total and LDL cholesterol increased (p less than 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.

Adult↗

Factor IX thrombogenicity: in vivo effects on coagulation activation and a case report of disseminated intravascular coagulation.

An episode of defibrination with bleeding following high dose Edinburgh Factor IX (D.E.F.IX) replacement in a patient with haemophilia B undergoing knee joint replacement is reported. We have also monitored plasma fibrinopeptide A levels in patients with haemophilia B following ten standard doses of D.E.F.IX (15-20 u/kg) and have been unable to document any change. Activation of the coagulation system, as previously noted, appears to be related to the use of Factor IX concentrates in high doses.

Adult↗

DDAVP stimulates prostacyclin production.

Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.

Animals↗

Beta-thromboglobulin and platelet counts - effect of malignancy, infection, age and obesity.

Plasma levels of beta-thromboglobulin (BTG) and platelet count were studied in 69 control subjects, 19 patients with operable abdominal malignancy, and 9 patients with acute bacterial infection. In control subjects there was a significant rise in BTG and fall in platelet count with age, and a negative correlation of BTG with obesity. BTG and platelet count were normal in patients with operable malignancy, but significantly increased in patients with acute bacterial infection. These effects must be considered in studies of BTG and thrombosis.

Adult↗

Increased blood viscosity and fibrinolytic inhibitor in type II hyperlipoproteinaemia.

Blood rheology and several haemostatic factors were studied in patients with type II hyperlipoproteinaemia (HLP) and matched controls. HLP patients had increased blood viscosity (p less than 0.01), the mean level being 18% higher at a low shear-rate (0.94 s-1) and 13% higher at a high shear-rate (94 s-1). The increased viscosity was due partly to a raised haematocrit (p less than 0.05), and partly to increased plasma viscosity (p less than 0.01) associated with increased plasma fibrinogen (p less than 0.02). Red cell deformability was normal, and viscosity was unrelated to either lipid or lipoprotein concentrations. Levels of the major fibrinolytic inhibitor. alpha 2-antiplasmin, measured by both functional and immunological techniques were higher in HLP patients (mean increase 30-32%). Plasminogen activator levels were normal in HLP patients and the ratio of fibrinolytic inhibitor to activator was therefore increased. Plasminogen concentrations were also increased. Levels of factor VIII activity and antigen, antithrombin III and anti-factor Xa activity, alpha 2-macroglobulin, platelet count, and platelet aggregation by adenosine diphosphate and adrenaline did not differ significantly in HLP patients and controls. These results suggest that the premature arterial disease associated with HLP may be related to increased blood viscosity, which reduces arterial blood flow, and increased alpha 2-antiplasmin, the major inhibitor of fibrinolysis.

Adolescent↗

Plasma fibrinopeptide A and beta-thromboglobulin in pre-eclampsia and pregnancy hypertension.

Increased plasma levels of beta-thromboglobulin (beta TG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in normal women, women taking oral contraceptives, normal pregnancy and pregnant women with hypertension or pre-eclampsia. No significant increases in beta TG or FPA were found in women taking oral contraceptives. Significantly increased concentrations of beta TG, but not FPA, were found in normal pregnant women in the second and third trimester of pregnancy when compared with non-pregnant age-matched controls. In eleven women with pregnancy hypertension and thirteen women with pre-eclampsia significantly elevated levels of both beta TG and FPA were found when compared with age, parity and gestation-matched pregnant controls. Although the mean value for both beta TG and FPA in the group with pre-eclampsia was higher than the group with pregnancy hypertension, the difference was not statistically significant. These findings provide additional evidence that pre-eclampsia and pregnancy hypertension are associated with activation of the coagulation system and the platelet release reaction.

Beta-Globulins↗

Prediction and selective prophylaxis of venous thrombosis in elective gastrointestinal surgery.

Clinical features were noted and routine and non-routine laboratory variables were measured before elective major gastrointestinal surgery in 63 patients aged 40 years or more. Deep-vein thrombosis (DVT), detected by routine 125I-fibrinogen leg scanning, developed in 21 patients. Five clinical variables but no laboratory variables were significantly associated with DVT: age; percent mean weight for age, sex, and height (%MW); presence of varicose veins; cigarette-smoking; and sex. The most useful discriminant index of these variables was age in years plus 1.3 x %MW. The index was validated prospectively in a further 41 patients, in 18 of whom DVT developed. The value of the index in selective prophylaxis was then assessed in a further 40 patients, of whom 24 (60%) with high-risk index received low-dose heparin (5000 units twice daily). DVT developed in 4 of the 40 patients, an incidence of 10% compared with the incidence of 37.5% (39 of 104) in the earlier studies with no prophylaxis.

Adult↗

Effects of the non-selective beta-adrenoceptor blocking agent, carteolol, on platelet function, blood coagulation and viscosity.

We have studied the effect of a new beta-adrenergic blocker, carteolol, on platelet function, blood coagulation and viscosity in 10 healthy male volunteers. Following carteolol (5 mg orally) we were able to demonstrate significant inhibition of platelet aggregation to ADP (p less than 0.05) and adrenaline (p less than 0.01) after 5 hours, but not at 2 or 24 hours. This maximum inhibition of platelet aggregation corresponded to peak plasma concentrations of carteolol measured. The platelet release reaction, as measured by plasma levels of the platelet specific protein beta-thromboglobulin (BTG) was unaltered and there was no significant effect on a panel of coagulation tests or on blood viscosity.

Adenosine Diphosphate↗

Endotoxemia, disturbance of coagulation, and obstructive jaundice.

A prospective study of coagulation disturbances and endotoxemia in 42 patients having major pancreatic or biliary surgery was performed. Endotoxin, soluble fibrin, and fibrin degradation products were measured before and after operation in 28 patients with obstructive jaundice and in 14 nonjaundiced controls. In the control group there was one death and no unexplained fever or postoperative hemorrhage. The jaundiced group had more complications: seven deaths, nine episodes of fever, and six episodes of hemorrhage. Soluble fibrin was detected only in patients with obstructive jaundice, in whom it occurred in 38 percent before operation. Positive endotoxin assay was as common in control patients as in the jaundiced group, but in the latter endotoxin was associated (p less than 0.05) with increased FDP and soluble fibrin. Patients with endotoxin or increased FDP levels before operation for jaundice carry a poor prognosis (7 of 11 died). Preoperative bowel preparation in 16 of the jaundiced patients did not affect the outcome.

Adult↗

Double-blind controlled clinical trial of ancrod for ischemic rest pain of the leg.

In a randomized double-blind trial, patients with ischemic rest pain of the leg received 8 days of treatment with intravenous injections of the defibrinating agent, ancrod (Arvin) or saline. Plasma fibrinogen, plasma viscosity, and blood viscosity were significantly reduced during ancrod therapy. After 27 patients had completed treatment, sequential analysis showed no preference for either therapy. In each group two-thirds of the patients claimed improvement in pain after treatment. There were no significant differences between treatment groups in analgesic consumption, Doppler systolic pressure ratio, or surgical intervention in the 6 months following treatment. We conclude that in patients with ischemic rest pain, ancrod therapy is not superior to placebo injections, and that the effect of placebo treatment is considerable.

Aged↗

Successful treatment of Raynaud's Syndrome with prostacyclin.

There is evidence to suggest that platelet activation occurs in Raynaud's syndrome. We evaluated the effect of prostacyclin (PGI2) a potent antiplatelet and vasodilator agent in 5 female patients with Raynaud's syndrome. Outpatient visits were made at weekly intervals for 4 weeks. At the first visit buffer solution (Wellcome Laboratories) was infused intravenously for 5 hrs, thereafter three five hr infusions of PGI2 at a peak dose of 10 ng/Kg/min were given. Six weeks after the infusions patients were reviewed. Symptomatic improvement, including healing of ischaemic ulcers, occurred in 4 out of 5 patients. Thermography confirmed an increase in hand temperature after PCI2. Subjective and objective improvement has persisted for at least 6 weeks after the last treatment.

Ambulatory Care↗