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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 253 records · Page 14Linked to original sources
PubMed1986

A haemorheological study of lignocaine.

Eight volunteers received lignocaine 75 mg i.m. Peak plasma lignocaine concentrations (mean 0.80 microgram ml-1; range 0.31-1.86 micrograms ml-1) were attained at 30 min. Haematocrit and red cell deformability remained unchanged. Lignocaine caused small but significant decreases in plasma viscosity and whole blood viscosity at both high and low shear rates (94 and 0.94 s-1). The small reductions in plasma viscosity and high shear blood viscosity observed ex vivo may be the result of alterations in plasma proteins. The reductions in low shear blood viscosity are considered to result from decreased red cell aggregation.

Adult↗
PubMed1986

Application of three intragenic DNA polymorphisms for carrier detection in haemophilia B.

In the west of Scotland use of a single intragenic restriction fragment length polymorphism (F9(VIII)/TaqI) allowed definitive genetic counselling for 45% of females at risk of being carriers for haemophilia B. Two further intragenic RFLPs, F9(VIII)/XmnI) and F9(VIII)/DdeI, have been applied to this population and by using all three polymorphisms the carrier status could be determined in 68% of females at risk. Linkage disequilibrium was apparent between these three RFLPs, and in the west of Scotland the single most clinically useful polymorphism was F9(VIII)/TaqI followed by F9(VIII)/DdeI and then F9(VIII)/XmnI. Overall, prenatal diagnosis by DNA analysis could be offered to 31 of 37 (84%) carriers (obligate and detected) in these families.

Cloning, Molecular↗
PubMed1986

Endothelial stimulation by DDAVP in von Willebrand's disease and haemophilia.

Desamino-D-arginine vasopressin (DDAVP) is known to stimulate factor VIII (FVIII) and plasminogen activator release from endothelial cells, and has been shown to stimulate prostacyclin (PGI2) production in normal and haemophilic subjects. In von Willebrand's disease (vWd) some patients have a dissociate response with regard to FVIII and plasminogen activator. The aim of our study was to compare the PGI2, FVIII and plasminogen activator response to DDAVP infusion in vWd with the response to DDAVP in normal and haemophilic subjects. PGI2 metabolites thromboxane B2 (TxB2), factor VIII coagulant activity, factor VIII-related antigen and plasminogen activator were measured before and after DDAVP infusion. There was a significant increase in PGI2 metabolites, factor VIII-related antigen and plasminogen activator in all groups following DDAVP, but no effect on TxB2 was found, and there was no evidence of any dissociate response to DDAVP in any of the groups. Basal levels of PGI2 metabolites, however, were significantly lower in vWd as compared to normal and haemophilic subjects. Post-DDAVP levels of PGI2 metabolites were also significantly lower in vWd as compared with normal subjects. This may be due to a reduced stimulus to PGI2 production in vWd secondary to defective platelet adhesion.

Antigens↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1985

Further studies on the role of red blood cells in spontaneous platelet aggregation.

The influence of red blood cells on platelet aggregation has recently been a subject of considerable interest. We have studied the effect of red cells on spontaneously formed platelet aggregates in rotating vials at 37 degrees C. Platelet aggregation was quantified by measuring the fall in number of single platelets with a whole blood platelet counter. Autologous packed red cells, platelet rich plasma and platelet free plasma were used to reconstitute aliquots of blood with constant platelet count but 0-60% haematocrit (Hct). The fall in platelet count was minimal at zero Hct, increased markedly with the Hct in the anaemic range and less markedly in the normal to polycythaemic ranges of Hct. Scanning electron microscopic observation of whole blood showed the presence of small platelet aggregates after about 3 mins rotation and very large aggregates after about 12 mins. ADP from red cells has been implicated in triggering platelet aggregation in whole blood. Whether aggregates are formed as a result of ADP leaking from the red cells or by their jostling physical action on the platelets is discussed. The marked effect of the red cells on spontaneous platelet aggregation however, justifies the manipulation of the Hct as a useful therapeutic option in the control of thrombotic and bleeding tendencies.

Adult↗
PubMed1985

Plasma beta-thromboglobulin, fibrinopeptide A and B beta 15-42 antigen in relation to postoperative DVT, malignancy and stanozolol treatment.

Plasma levels of betathromboglobulin (BTG), fibrinopeptide A (FPA) and B beta 15-42 fragment, indices of platelet release, thrombin generation and plasmin activity respectively, were measured in 32 high risk patients during a double blind study of a single dose of the anabolic steroid stanozolol (50 mg IM) in the prevention of DVT after major gastro-intestinal surgery. The prevalence of malignancy and the incidence of DVT (125I fibrinogen scan) were similar in the two treatment groups. On the first postoperative day, BTG, FPA and B beta 15-42 levels were increased in most patients. Plasma BTG levels were significantly increased on the first post-operative day in patients who developed a DVT (n = 14) compared to those patients who did not (n = 18). A significant increase in FPA levels was found in the DVT group, 7 days after surgery. On the morning before surgery, plasma B beta 15-42 levels were significantly increased in patients who developed a DVT. In patients undergoing surgery for early malignancy (n = 17), we observed a pre-operative increase in FPA levels when compared to patients without malignancy. At post-operative day 7, B beta 15-42 levels were significantly increased in patients who received stanozolol (n = 15), when compared to the placebo group, suggesting that intramuscular stanozolol increases fibrinolysis in vivo.

Beta-Globulins↗
PubMed1985

Increased prostacyclin metabolites and decreased red cell deformability in patients with systemic sclerosis and Raynauds syndrome.

Patients with systemic sclerosis (SS) often suffer from Raynaud's Syndrome (RS). As prostacyclin (PGI2) is of benefit in the treatment of RS in SS, we have measured endogenous stable metabolites of PGI2 (PGI2m) in 42 patients with Raynaud's Phenomenon (RP) of varying aetiology (15 SS patients, 15 patients with Raynaud's Disease (RD) but no other symptoms, and 12 other RS patients with probable connective tissue disorder). Results were compared with 15 matched controls. Since abnormally rigid red blood cells (RBC) may occur in SS, we also measured RBC deformability (filtration technique). Results show that the SS group have significantly elevated PGI2m levels compared to patients with RD alone and normal controls. In addition, SS patients have more rigid RBC. If all 42 patients with RS were analysed, a significant correlation between PGF and RBC filtration was obtained. The cells of SS patients are resistant to the effects of PGI2 and it would appear that as a compensatory mechanism, production of PGI2 is increased. Treatment with exogenous PGI2 may overcome this resistance and improve microcirculatory flow. The more rigid RBC in SS may also be related to the increased endogenous PGI2. These results may have important clinical implications and allow new therapeutic approaches.

6-Ketoprostaglandin F1 alpha↗