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Biomedical subjects

C D Forbes

Publications and source records attributed to C D Forbes.

At least 109 records · Page 6Linked to original sources

Effect of insulin therapy on coagulation and platelet function in type II (non-insulin-dependent) diabetes mellitus.

Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes.

Aged↗

Liver dysfunction in haemophilia.

Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.

Adult↗

Immunosuppression following alloantigen exposure: a role for lymphocyte Fc gamma-receptor blocking antibodies.

In this study we have shown that IgG class, noncytotoxic, Fc gamma-receptor blocking antilymphocyte antibodies can de detected in a high proportion of patients who have previously been exposed to alloantigens, i.e. multiple transfused uraemic patients, haemophiliacs and male homosexuals. These antilymphocyte antibodies appear to cross-react with human spermatozoa. Monomeric IgG preparations from these patients were also found to significantly impair T-cell responsiveness in vitro. Depression of cell mediated immunity by these antibodies may contribute to prolonged graft survival in uraemic patients but may also predispose to infection.

Acquired Immunodeficiency Syndrome↗

HLA antigens in haemophilic arthritis: a family study.

HLA typing for antigens of the A, B, C, and DR loci was carried out on lymphocytes from a haemophilic (Type A) family which included four siblings with arthritis. No single haplotype was found to relate to the presence of haemophilia or haemophilic arthritis.

Adult↗

The effect of increasing fibrinolysis in patients with rheumatoid arthritis: a double blind study of stanozolol.

Fibrin deposition in rheumatoid arthritis may be responsible for some of the clinical manifestations of the disease. It has been shown that in severe rheumatoid arthritis fibrinolysis is decreased but can be stimulated using the fibrinolytic enhancing agent stanozolol. A prolonged increase in fibrinolysis may decrease joint fibrin deposition and lead to clinical improvement and we have therefore investigated stanozolol as a therapeutic agent. Forty patients were enrolled. Twenty patients received stanozolol 5 mg twice daily for six months and 20 received a matching placebo. Assessment of disease activity was made in the conventional way. Results show that the two groups were comparable. After six months nine of the control patients had withdrawn because of drug ineffectiveness compared with two stanozolol patients, and five control patients felt they had improved compared with 15 stanozolol patients. Disease activity had significantly decreased by the end of the study in the treated group, and detailed analysis showed improvement in ESR, articular index, duration of morning stiffness and visual analogue pain scale. We suggest that stanozolol may be of value in rheumatoid arthritis although this pilot study has looked at only small numbers of patients over a short period.

Arthritis, Rheumatoid↗

Increased blood viscosity in diabetic proliferative retinopathy.

Blood rheology and haemostasis were assessed in 18 diabetics with proliferative retinopathy and in 18 diabetics without proliferative retinopathy, matched for age, sex, smoking habit and type, duration and treatment of diabetes. Proliferative retinopathy was associated with significantly higher levels of blood viscosity at high and low shear rates, which were related to higher levels of plasma viscosity and fibrinogen. Blood urea, glucose, glycosylated haemoglobin and white cell count were also significantly higher, whereas haematocrit, red cell deformability and several other haematological and biochemical variables did not differ significantly in the 2 groups. In view of these findings, and of our recent demonstration that increased blood viscosity also exists in those patients with retinal vein occlusion who develop a similar proliferative retinopathy, we suggest that hyperviscosity may contribute to retinal ischaemia and hence proliferative retinopathy.

Adult↗

Haemophilic arthritis.

A detailed clinical and radiological examination of the joints and laboratory studies were carried out on 139 haemophiliacs attending a single centre. The group included more patients with mild and moderate haemophilia (factor levels 6 to 60 per cent) than in previous studies. Haemarthrosis, the most common bleeding manifestation, had affected more than two-thirds of patients including many with mild or moderate disease. Restriction and contracture of the knees and elbows were the most common clinical features and, with the ankles, these joints were most frequently affected both clinically and radiologically. Using a combination of clinical and radiological features, 42 per cent of the patients could be classed as having 'definite' and a further 14 per cent 'possible' haemophilic arthritis. Although haemarthroses were equally prevalent in patients with classical haemophilia and Christmas disease, arthritis was more frequently present in the former. Haemarthrosis and joint disease were exceptional in von Willebrand's disease. The prevalence of arthritis generally related to disease severity as measured by factor level but, in contrast to earlier studies, definite arthritis was seen in some patients with factor levels up to 20 per cent of normal although the number of affected joints was less in these patients with milder disease. Laboratory test abnormalities including circulating immune complexes and hypocomplementaemia were noted in some patients but the abnormalities correlated poorly with clinical features. The present results suggest a recent slight reduction in the prevalence or severity of haemophilic arthritis, possibly attributable to recent improvements in factor replacement treatment. Longer-term studies are required to show whether arthritis is indeed lessening or whether the onset is merely being delayed.

Adolescent↗

Inhibition of platelet aggregation in whole blood by adrenoceptor antagonists.

It has recently become possible to study platelet aggregation in whole blood which may more closely resemble the in-vivo situation as the platelets are left in their natural milieu with red and white cells present which themselves can influence aggregation. The effects of 4 adrenoceptor antagonists on platelet aggregation in whole blood were studied in-vitro using the Clay-Adams Ultra Flo 100 whole blood platelet counter. Labetalol, pindolol and propranolol inhibited aggregation to 0.5 microgram/ml collagen in a dose dependent manner, and were synergistic with prostacyclin in inhibiting collagen induced aggregation. These 3 drugs also promoted reversal of aggregation induced by 10 microM ADP, but only inhibited 0.5 mM arachidonic acid induced aggregation at high drug concentrations. Atenolol had no effect on either collagen, ADP or arachidonic acid induced aggregation. The anti-platelet effect of these drugs may be of value in the treatment of vascular disease.

Adenosine Diphosphate↗

Protein C antigen levels in major abdominal surgery: relationships to deep vein thrombosis, malignancy and treatment with stanozolol.

Activated protein C is a potent inhibitor of coagulation, and familial protein C deficiency has been associated with recurrent venous thrombosis. We have investigated protein C antigen levels in patients undergoing major elective abdominal surgery, to determine their relationships to postoperative deep vein thrombosis (DVT), malignancy, and preoperative treatment with intramuscular or oral stanozolol. Preoperative and postoperative protein C levels were not significantly different in patients with and without DVT (detected by 125I-fibrinogen leg scans), nor in patients with and without malignancy. In a placebo group (n = 26), a significant fall in protein C was maximal on the first postoperative day and persisted for 7 days. In a group given intramuscular stanozolol, 50 mg on the preoperative day (n = 23) stanozolol shortened the duration of the postoperative fall in protein C, but did not prevent DVT. In a group given oral stanozolol, 10 mg/day for 2 weeks before and 1 week after operation (n = 11), stanozolol significantly increased protein C levels prior to surgery, hence maintaining protein C at pretreatment levels after surgery. The effect of this regimen on the incidence of DVT is under study.

Adult↗

White blood cell count and haematocrit as predictors of coronary recurrence after myocardial infarction.

Baseline white blood cell count (WCC) and haematocrit were examined in relation to recurrent coronary events and to all-cause mortality in 2026 persons enrolled in the first Persantin-Aspirin Reinfarction Study (PARIS-1) 2-60 months after myocardial infarction. WCC was strongly related to coronary recurrence (relative risk 3.5 for men with WCC greater than or equal to 9 X 10(9)/l vs men with WCC less than 5 X 10(9)/l) and total mortality (relative risk 2.6). No such relationships were found for haematocrit. WCC correlated also with cigarette-smoking, diuretic use, serum cholesterol and uric acid; however, the associations with coronary recurrence and total mortality persisted on multiple linear and logistic regression analysis including these variables and treatment group (p less than 0.001). WCC is therefore an easily-measured prognostic variable in survivors of myocardial infarction. Furthermore, we suggest that white blood cells may promote myocardial ischaemia by capillary plugging and/or release of toxic oxygen metabolites.

Adult↗

A comparative study of the effects of adrenoceptor antagonists on platelet aggregation and thromboxane generation.

Platelet aggregation and thromboxane A2 have been implicated in the pathogenesis of several forms of vascular disease. The aim of this study was to determine the effect of a wide range of adrenoceptor antagonists on platelet aggregation, and thromboxane A2 production, from normal human platelet rich plasma in vitro. Labetalol, pindolol and propranolol inhibited platelet aggregation to collagen in a dose dependent manner. Increasing the concentration of collagen "shifted" the dose response curve to the right. These 3 drugs also significantly inhibited thromboxane A2 generation in response to collagen but not to arachidonic acid. This effect was independent of any inhibitory effect of these drugs on platelet aggregation, and occurred at a drug concentration close to that obtained in vivo. Atenolol, metoprolol, prazosin and timolol were similarly assessed but had no effect on either platelet aggregation or thromboxane A2 generation. This ability of labetalol, pindolol, and propranolol to inhibit platelet aggregation and thromboxane generation, may be of clinical benefit in view of the increasing evidence implicating thromboxane A2 in the pathogenesis of vascular disease.

Adrenergic beta-Antagonists↗

Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double blind study.

Prostaglandin E1 (PGE1) and prostacyclin have been used in Raynaud's phenomenon (RP) but are unstable and require intravenous administration. An alternative approach is to stimulate the body's own PGE1 production via administration of the precursor essential fatty acid. We studied the effect of 12 capsules/day of evening primrose oil (EPO) on the manifestations of RP. 21 patients received a two week course of placebo, thereafter 11 received EPO for 8 weeks and 10 patients received placebo. As the weather worsened the placebo group experienced significantly more attacks than the EPO group. Visual analogue scales assessing the severity of attacks and coldness of hands improved in the EPO group. No changes were seen in either group in hand temperatures and cold challenge plethysmography. Blood tests showed some antiplatelet effects of the drug. In conclusion patients receiving EPO benefited symptomatically. This was not matched however by any change in objective assessment of blood flow, although changes in platelet behaviour and blood prostanoids were observed.

Cold Temperature↗

Effect of stanozolol on factors VIII and IX and serum aminotransferases in haemophilia.

The treatment of haemophilia has been dramatically improved since the introduction of factor VIII and IX concentrates, however these concentrates have brought new problems such as hepatitis and A.I.D.S. An oral agent which could raise endogenous levels of factor VIII and IX would be of great benefit. Danazol, an anabolic steroid, has recently been shown to increase levels of factors VIII and IX in haemophilia. We therefore studied the effect of stanozolol, a closely related anabolic steroid, in 15 patients with haemophilia A or Christmas disease over a 2-4 week period. There was no consistent change in factor VIIIc or factor IX, and fibrinolysis was significantly enhanced. No effect was apparent on the incidence of spontaneous bleeds. However serum aminotransferases which were abnormal in 11 of the 15 patients at the start of the study fell significantly with stanozolol therapy. This raises the interesting possibility that anabolic steroids may be beneficial in patients with chronic liver diseases.

Blood Viscosity↗