Search PubMed⌕ Search

Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 163 records · Page 9Linked to original sources

The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers.

There is an increased frequency of arterial thrombosis in cigarette smokers. The changes in blood coagulation seen in these subjects have been studied by many workers but results have not always been in agreement. We wished to study the effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in ten habitual smokers, and to compare these results with non-smoking controls. Results show that the smoking group had higher plasma fibrinogen (p less than 0.04), lower plasminogen (p less than 0.02) and plasminogen activator (p less than 0.05), and higher plasma viscosity (p less than 0.003). The changes seen in cigarette smokers after smoking three cigarettes were an increase in the rate of platelet aggregation to ADP (p less than 0.02), an increase in alpha 2M, (p less than 0.02), and factor VIII RAG (p less than 0.05). Plasma viscosity was decreased (p less than 0.02) as was red cell deformability (p less than 0.02). We confirm an increased tendency to hypercoagulability in smokers compared to controls which becomes more pronounced immediately after smoking three cigarettes.

Adult↗

A double-blind trial of intramuscular stanozolol in the prevention of postoperative deep vein thrombosis following elective abdominal surgery.

Fibrinolytic shutdown may be important in the development of postoperative deep vein thrombosis (DVT). We have previously shown that stanozolol 50 mg, given intramuscularly 24 hr before surgery, prevents the decrease in plasminogen activator activity (PA) seen on the first postoperative day in patients at high risk of DVT. To investigate the role of fibrinolytic shutdown in causation of DVT, sixty patients were randomized in a double-blind controlled trial to receive stanozolol or placebo intramuscularly, and DVT was detected by leg scanning and confirmed by venography. Scan positive DVT occurred in 11 of 31 placebo patients (35%) and 12 of 29 who received stanozolol (41%). A significant decrease in PA was confirmed in the placebo group, while stanozolol caused a significant increase in PA on the first postoperative day. Patients in either group who did not develop DVT showed minimal changes in PA. We conclude that prevention of fibrinolytic shutdown by this regimen of stanozolol does not prevent postoperative DVT, and that further studies are required to clarify the relationship of postoperative fibrinolysis and DVT.

Abdomen↗

Response of femoral venous oxygen tension to graduated pressure stockings--possible relationship to deep vein thrombosis.

Venous oxygen tension (pO2) was measured in discrete samples of blood obtained through the femoral vein of cardiac catheterisation patients before, during and after application of sustained external graduated pressure in the form of compression stockings (T. E. D. Kendall). There was a significant reduction (p less than 0.05) of pO2 from the baseline value both 30 sec and one minute after the application of the pressure stockings. Thereafter, the pO2 rose to baseline values. Two minutes after the stockings were removed there was again a significant reduction (p less than 0.05) of pO2 from the baseline value. We suggest that the decrease in venous pO2 on application of external pressure may be a reflection of washing out of stagnant hypoxic blood from the venous valve pockets, which may be related to the formation of deep vein thrombosis (DVT).

Blood Gas Analysis↗

A comparison of spontaneous platelet aggregation in whole blood with platelet rich plasma: additional evidence for the role of ADP.

ADP, generated from red blood cells is believed to be responsible for the spontaneous aggregation of platelets in whole blood. This notion is based mainly on the use of enzymes which remove ADP. We have studied spontaneous platelet aggregation in whole blood and autologous platelet rich plasma obtained from 12 healthy male and female volunteers. Platelet aggregation was quantitated by measuring the fall in the number of single platelets counted using a whole blood platelet counter (Ultra Flo 100). In a rotating tube model, the mean fall in the number of platelets due to spontaneous aggregation was 56% in whole blood but, only 3% in platelet rich plasma prepared from the same blood samples. Spontaneous platelet aggregation in whole blood was unaffected by apyrase grade I, but was reduced to 15% by apyrase grade II, to 38% by creatine phosphokinase/creatine phosphate and to 9% by pyruvate kinase/phosphoenolpyruvate. The results of this study provide additional evidence that ADP generated in whole blood triggers the spontaneous aggregation of platelets.

Adenosine Diphosphate↗

Protein C, an anticoagulant protein, is increased in healthy volunteers and surgical patients after treatment with stanozolol.

On both oral and intramuscular administration, the anabolic steroid stanozolol was found to increase protein C antigen concentrations in circulating blood. In fourteen healthy young volunteers (who received stanozolol orally, dose 10 mg/day) the average increase was 1.5-1.6 times the normal concentrations after 3-6 weeks' treatment and was accompanied by more moderate increases in the other vitamin K-dependent factors II, IX and X to 1.4, 1.4 and 1.2 times their normal concentration respectively. However, there was no change in factor VII. In sixteen elderly surgical patients, intramuscular injection (50 mg) one day prior to surgery induced a moderate increase within 24 hours (to 1.11 times the pretreatment concentration) and seven days after operation (to 1.19 times), and reduced the postoperative fall in protein C. Stanozolol administration seems to be a promising pharmacological method for increasing anticoagulant protein C levels in congenital and acquired deficiencies.

Adult↗

The consumers' views of genetic counseling of hemophilia.

Twenty-five Scottish and 22 Canadian patients with hemophilia, and 15 Scottish and 14 Canadian carriers of hemophilia participated in the study. They were interviewed with respect to their experience of and attitudes to genetic counseling, perceptions of the counselor's role, and satisfaction with existing care for families with hemophilia. Most patients and carriers favor genetic counseling as part of general counseling offered to them by the hemophilia center and think that such counseling should include dealing with such issues as schooling, employment, emotions, and psychological problems. Prenatal testing and termination of pregnancy is at present unacceptable to most of the participants, although they do not object to the use of these methods in cases of illnesses more severe than hemophilia.

Abortion, Eugenic↗

Effect of stanozolol on delta-aminolaevulinic acid synthase and hepatic monooxygenase activity in man and rat.

Stanozolol is an anabolic steroid which is used in the treatment of aplastic anaemia and has been recently advocated for the prophylaxis of vascular thrombosis. Similar steroid substances stimulate the activity of delta-aminolaevulinic acid synthase (ALA S), the rate limiting enzyme of haem biosynthesis, in rat hepatocytes and chick embryo liver cell cultures and activate acute hepatic porphyria. In the present study stanozolol (10 mg daily for 14 days) has been shown to increase significantly leucocyte ALA S activity in 9 healthy male subjects. There was a concomitant rise in urinary ALA and total porphyrin excretion but no change in antipyrine kinetics or urinary 6 B hydroxycortisol excretion. In a complementary study in male Sprague Dawley rats, stanozolol administered intraperitoneally, produced a dose-dependent increase in hepatic ALA S activity without changing hepatic cytochrome P 450 content. Stanozolol has been clearly shown to elevate ALA S activity, probably directly, and thereby, porphyrin production without affecting hepatic monooxygenase activity. This porphyrinogenic effect may be relevant to the successful treatment of aplastic anaemia with anabolic steroids. Leucocyte ALA S activity may provide a human system for the study of drug porphyrinogenicity in vivo.

5-Aminolevulinate Synthetase↗

The effects of intravenous ZK36-374, a stable prostacyclin analogue, on normal volunteers.

Prostacyclin (PGI2) therapy has been evaluated in many vascular diseases. However, it is unstable and a potent vasodilator, able to lower blood pressure. Although such effects may be desirable in some situations, they are unwanted in others. ZK36-374 (Schering AG) is a carbacyclin derivative with a similar action to PGI2; however, it is chemically stable and has less of a hypotensive action. We evaluated the effects of a 4-hour I.V. infusion of ZK36-374 at a maximum dose of 2ng/Kg/min. in ten normal volunteers. Prior to the infusion and at 2 and 4 hours, blood was sampled for estimation of platelet aggregation in both platelet rich plasma and whole blood. Beta-thromboglobulin, 6-keto-PGF1 alpha and TXB2 were measured by radioimmunoassay, as were other coagulation and rheological tests. The infusion was well tolerated with facial flushing, jaw trismus and some nausea at max dose. Blood pressure and pulse rate were not significantly altered. During infusion of ZK36-374, the rates of platelet aggregation to 2 microns ADP and 2 micrograms collagen in PRP were significantly decreased when compared to baseline, as was whole blood aggregation to 2 microns ADP and 0.5 microgram collagen. Beta TG also fell significantly, as did the levels of 6-keto-PGF1 alpha and TXB2. Fibrinolysis, blood viscosity, and red cell deformability were unchanged. ZK36-374 is an effective anti-platelet agent without major toxic or hypotensive effects.

Adult↗

The relationship of plasma and serum viscosity to disease activity and smoking habit in rheumatoid arthritis.

Viscosity measurements of serum and plasma have been suggested as improvements on other indicators of activity in the rheumatic diseases. We compared the clinical assessment of disease activity in 71 patients with rheumatoid arthritis against various laboratory tests including viscosity measurements. The effects of smoking were also studied. While many of the tests showed correlations with each other, none was found to correlate with any of the clinical parameters. Smoking lowered the ESR, but did not affect the plasma viscosity in these patients. Thus viscosity measurements were no improvement in assessing activity in a cross section of patients, though its lack of dependence on smoking habit may be an advantage in sequential studies.

Arthritis, Rheumatoid↗

The correlation of clinical assessment of synovial fluid with its measured viscosity.

The viscosity of 10 specimens of rheumatoid synovial fluid was assessed using side-room tests as well as being measured in a viscometer. All of the tests, and particularly the 'mucin clot', correlated well with measured viscosity. We conclude that the mucin clot test does indeed reflect viscosity and can demonstrate the presence of inflammatory joint disease.

Arthritis, Rheumatoid↗

Alteration of hormone levels in normal males given the anabolic steroid stanozolol.

Anabolic steroids have widespread metabolic effects but, to date, their proven clinical indications have been limited. Recently the 17 alpha-alkylated steroid, stanozolol, has been shown to be of value in a variety of commonly occurring vascular diseases. Its endocrine effects have received little attention and we have investigated the effect of administering a 14 d course of stanozolol (10 mg orally per day) on a variety of important hormonal pathways in nine healthy male subjects. Significant changes occurred as follows: a 55% reduction in serum testosterone levels was noted and was accompanied by reductions in 'derived' free testosterone, sex hormone binding globulin and LH levels; total T4 and T3 levels fell in association with a decrease in thyroxine binding globulin, but no alteration was detected in TSH or free T4 levels. Changes in vitamin D status, with falls in 25-hydroxycholecalciferol and vitamin D binding globulin were also observed. These effects were reversible on stopping treatment. Stanozolol therapy therefore leads to a number of hormonal changes, probably by an action at both pituitary and hepatic levels.

Adult↗

The use of tools by children with haemophilia.

Eight mothers with their 3.1- to 5.7-year-old children with haemophilia and eight control mothers with their children were videotaped while playing three games using a knife, a pair of scissors and a wooden hammer, and two games without tools. Although the children with haemophilia were less proficient, took less care, and were more excited when handling sharp tools than the control children, their mothers did not correct their children when they used a knife incompetently and carelessly. It is recommended that counselling should emphasize the deliberate preparation and training of the haemophilic child in the use of tools which are potentially dangerous.

Adaptation, Psychological↗

Blood rheology in pre-eclampsia and intrauterine growth retardation: effects of blood pressure reduction with labetalol.

Blood viscosity ( Contraves L S 30) and its determinants were measured in 23 patients with mild/moderate pre-eclampsia, 10 patients with intrauterine growth retardation and 22 control subjects, matched for age and gestation. Both abnormal groups had a significantly increased blood viscosity at high shear rate (94 s-1) associated with increased haematocrit. Fibrinogen levels were also increased, but there were no significant differences between groups in plasma viscosity, low shear viscosity (0.94 s-1) or red cell deformability, measured by a low-shear washed cell system of filtration through 5-micron pore diameter Nuclepore filters. In the pre-eclamptic group, measurements were repeated after 1-2 weeks in nine patients treated with labetalol (a combined alpha and beta adrenergic blocker) and in 10 patients treated with bed rest. Labetalol reduced blood pressure but no change in rheology was seen in either group. Control of blood pressure by labetalol does not adversely affect rheology, in contrast to diuretics which are known to cause haemoconcentration and increased blood viscosity.

Adult↗

Decreased plasma fibrinolysis in patients with rheumatoid arthritis.

We have investigated the fibrinolytic status of 56 patients with rheumatoid arthritis (RA). Plasma fibrinogen and plasminogen were significantly elevated. Levels of these two substrates, along with alpha 2 macroglobulin and antithrombin III correlated with disease activity. Plasminogen activator (PA) activity was decreased in patients with severe disease. Twelve patients were given stanozolol, a fibrinolytic enhancing agent, for two months as a test for endothelial production of plasminogen activator. This caused a significant increase in blood plasminogen and PA activity. Five patients received a two-week course of stanozolol with joint aspiration before and after. Joint plasminogen levels were increased. We suggest that inadequate fibrinolysis occurs in RA, and that this may contribute to some of the pathological features of the disease. It is possible to stimulate both blood and joint fibrinolysis by stanozolol. A more prolonged increase in plasminogen activator activity might decrease joint fibrin deposition, and stanozolol should be investigated as a therapeutic agent in RA.

Antithrombin III↗

Blood coagulation and platelet function following maximal exercise: effects of beta-adrenoceptor blockade.

Alterations of platelet function and blood coagulation may occur with exercise or beta-adrenoceptor blockade. To determine if beta-blockade could modify exercise-induced changes in haemostatic factors we performed a double-blind study of acute strenuous exercise in normal males with and without beta-blockade. Exercise increased prostacyclin and plasminogen activator levels but there was no evidence of thrombin generation as indicated by unchanged platelet aggregation responses, beta-thromboglobulin and fibrinopeptide A levels. The only alteration in coagulation by beta-blockade was a reduction in the factor VIII:C and VIII:RAg rise after exercise and this modification may be relevant to the protective effect of these drugs in patients with coronary artery disease.

Adrenergic beta-Antagonists↗

Effect of prostacyclin (epoprostenol) on the aggregation of human platelets in whole blood in vitro.

Prostacyclin (PGI2) is a potent endogenous inhibitor of platelet aggregation. The effect of PGI2 on platelet aggregation and disaggregation in whole human blood was studied at 37 degrees C in vitro. Aggregation or disaggregation was quantified by counting single platelets using the recently developed Ultra Flo 100 Whole Blood Platelet Counter. Aggregation of platelets in whole blood was induced by arachidonic acid (AA, 400 microM), adenosine 5'-diphosphate (ADP, 10 microM), thrombin (0.1 U/ml) and collagen (1 microgram/ml). At peak aggregation, each aggregating agent induced about a 90% fall in the number of single platelets counted. When whole blood was pre-incubated with PGI2 (0.5-8 nM), it dose dependently inhibited aggregation of platelets induced by all four aggregating agents. Platelet aggregates induced by ADP or thrombin could rapidly be disaggregated by PGI2 added to blood at peak aggregation. Disaggregation of collagen-induced platelet aggregation by PGI2 was slow and minimal and it was completely ineffective in disaggregating AA-induced platelet aggregates. Unlike platelet-rich plasma, which is routinely used to study platelet aggregation, the present whole-blood method allows red and white blood cells to exert their influences on platelet function, and is an important step towards a physiological state for evaluating the effects of pharmacological agents on platelets in whole blood in vitro and ex vivo.

Adenosine Diphosphate↗

Effects of diabetic control and biosynthetic human insulin on blood rheology in established diabetics.

Blood rheology (blood viscosity, haematocrit, plasma viscosity, erythrocyte sedimentation and deformability) was measured in 22 diabetics in a study to compare animal insulins with biosynthetic human insulin. All rheological variables were significantly abnormal in the diabetics when compared with matched normal controls, and were not influenced by the type of insulin injected. However, blood rheology was related to diabetic control, as judged by glycosylated haemoglobin levels; when diabetic control was worst (mean glycosylated haemoglobin 11%), blood viscosity was significantly higher and red cell deformability significantly lower than when control was at its best (mean glycosylated haemoglobin 9.5%). A similar correlation between mean red cell deformability and mean glycosylated haemoglobin was found when individual diabetics were compared (r = 0.66; p less than 0.001). The occurrence of abnormal blood viscosity and red cell deformability during periods of poor diabetic control may contribute to the development of diabetic vascular complications.

Adolescent↗