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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 235 records · Page 13Linked to original sources
PubMed1987

Blood rheology in general medicine and surgery.

Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication.

Blood Flow Velocity↗
PubMed1987

The consequences of early marriage on marital dissolution.

This study is concerned with the negative effects of early marriage on marital stability. "The focus on this paper is an analysis of a path model which includes the estimated effects of antecedents of early marriage, early marriage and education on the probability of divorce. Findings using the [U.S.] General Social Surveys support research that suggests that early marriage is the most important varialbe influencing divorce. Further, little influence of the early marriage measure through education was found."

Americas↗
PubMed1987

Antithrombin III Glasgow: a variant with increased heparin affinity and reduced ability to inactivate thrombin, associated with familial thrombosis.

A functional antithrombin III (AT III) deficiency has been identified in two generations of a family with a high incidence of thrombosis. The deficiency presented as approximately 50% reduction in heparin cofactor activity compared to its antigen concentration. No abnormality was detected by crossed immunoelectrophoresis in the presence or absence of heparin. Plasma from the propositus was precipitated with dextran sulphate, applied to heparin-Sepharose and the AT III stepwise eluted with NaCl. The AT III had a reduced ability to inactivate thrombin, when this was monitored by substrate hydrolysis or by SDS polyacrylamide gel electrophoresis. Its mobility was normal by the latter technique using 10-20% gradient gels under reducing and non-reducing conditions. AT III from the patient was reapplied to heparin-Sepharose and eluted with a NaCl gradient. An active pool eluted in the same NaCl concentration range used to purify normal AT III, while predominantly inactive AT III eluted at higher NaCl concentrations. It is concluded that this variant, designated AT III Glasgow, has increased affinity for heparin but reduced ability to inactivate thrombin.

Antithrombin III↗
PubMed1987

Comparison of inhibitory actions of prostacyclin and a new prostacyclin analogue on the aggregation of human platelet in whole blood.

Prostacyclin (PGI2), an unstable endogenous prostanoid, is a potent vasodilator and inhibitor of platelet aggregation. The use of exogenous PGI2 as an antithrombotic agent is limited by its chemical instability and lack of dissociation between its vasodilatory and antithrombotic actions. Iloprost (ZK36374) is a recently developed, chemically stable, carbacyclin analogue of PGI2. Preliminary evaluation studies have shown a significant dissociation between vasodilatory and antithrombotic actions of Iloprost. We have compared the effects of PGI2 and Iloprost on platelet aggregation in human whole blood. Platelet aggregation was induced by ADP (4 microM), adrenaline (Adr, 0.4 microM) and arachidonic acid (AA, 0.4 mM). Aggregation was quantified as a fall in the number of single platelets counted using the Clay Adams Ultra Flo 100 whole blood platelet counter. In the absence of any PGI2 or Iloprost, each aggregating agent induced up to an 80% fall in the number of single platelets counted. When blood was pre-incubated with PGI2 (1-6 nM) or Iloprost (1-6 nM), aggregation responses to all three aggregating agents were inhibited in a dose-dependent manner. Iloprost was equipotent to PGI2 against ADP-induced aggregation but was more potent than PGI2 against Adr- and AA-induced aggregation. It is concluded that Iloprost, as a chemically stable PGI2 analogue, may be superior to PGI2 as an antithrombotic agent.

Adenosine Diphosphate↗
PubMed1987

Severity of coronary artery disease and basal fibrinolysis.

Basal venous blood levels of several components of the fibrinolytic enzyme system (plasminogen activator, plasminogen, fibrin degradation products, alpha 2-antiplasmin, and alpha 2-macroglobulin) were measured in 100 white men with angiographically defined coronary artery disease. The tests of fibrinolysis were not related to the severity of coronary artery disease, as indicated either by the number of vessels involved or by a coronary score system. Fibrinogen levels, however, did show a modest association with the extent of coronary atheroma (r = 0.21, p less than 0.05). Triglyceride levels were associated with the inhibitors of fibrinolysis: positively with alpha 2-antiplasmin (r = 0.31, p less than 0.005) and negatively with alpha 2-macroglobulin (r = -0.25, p less than 0.05). The alpha 2-antiplasmin levels were significantly elevated in patients with hypertriglyceridaemia. Neither smoking nor beta-blockade had any effect on the tests of fibrinolysis. This study adds support to the association of plasma fibrinogen with ischaemic heart disease.

Adult↗
PubMed1987

The effect of exercise on thrombin and plasmin generation in middle-aged men.

Plasma levels of B beta 15-42 peptide and fibrinopeptide A (FPA) were measured as indicators of plasmin-mediated fibrin(ogen)olysis and thrombin activity of fibrinogen in 34 middle-aged men, at rest and following a standard exercise test. In the group as a whole no significant changes in B beta 15-42 or FPA were noted after exercise. When the group was subdivided into men with (n = 20) and without (controls n = 14) coronary heart disease, exercise-stimulated thrombin and plasmin generation was found only in the control group who exercised for a significantly longer duration. The rise in B beta 15-42 was related to both the intensity and duration of exercise. Similar increases in plasma fibrinolytic activity (fibrin plate) occurred in both groups and no other differences in the components of the fibrinolytic system (plasminogen, alpha 2-antiplasmin, fibrin degradation product) were noted either after exercise or between the groups. Exercise in normal middle-aged men is associated with modest thrombin and plasmin activation.

Adult↗
PubMed1987

Haemophilia, blood products and HIV infection.

Between 1979 and 1984, many haemophiliacs in the UK were exposed to the human immunodeficiency virus (HIV) by transfusion of blood products, in particular clotting factor concentrates, especially those imported from the USA. In the UK 1025 haemophiliacs are HIV-antibody-positive, of whom 75 are in Scotland. Thirty-one UK haemophiliacs have developed the Acquired Immune Deficiency Syndrome (AIDS), of whom 23 have died. The clinical progress of HIV infection appears similar in haemophiliacs and in other risk groups, except that Kaposi's sarcoma is rare. There is evidence that transfusion of blood products is immunosuppressive in the absence of HIV antibody. Blood donor selection and heat treatment of clotting factor concentrates were introduced from 1985, and so far these measures appear to have largely prevented new HIV infection in haemophiliacs. Meanwhile a tragic toll of iatrogenic disease and death continues to increase.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Therapeutic potential of choline magnesium trisalicylate as an alternative to aspirin for patients with bleeding tendencies.

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p less than 0.005), AA (p less than 0.01) and spontaneous aggregation (p less than 0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

Adolescent↗
PubMed1987

Thrombin and plasmin activity in diabetes mellitus and their association with glycaemic control.

Abnormalities of haemostasis are common in diabetes mellitus. As indicators of fibrinolysis and coagulation, plasmin and thrombin activity were assessed by assay of the fibrinogen peptide derivatives B beta 15-42 and fibrinopeptide A respectively in 60 diabetic patients and 50 control subjects in a cross-sectional study. Glycosylated haemoglobin (HbA1) correlated with B beta 15-42 (r = -0.26, p less than 0.05) and fibrinopeptide A (r = 0.30, p less than 0.05) in the diabetic patients suggesting that poor glycaemic control (i.e. high HbA1 levels) was associated with depressed plasmin and enhanced thrombin activity. Compared to controls, fibrinopeptide A levels were increased in diabetics (p less than 0.001) irrespective of sex or type of diabetes. B beta 15-42 levels were normal in diabetic females but increased in diabetic men (p less than 0.001) possibly secondary to the activation of coagulation. These results suggest that in diabetes mellitus activation of coagulation is the dominant haemostatic abnormality and that better glycaemic control could influence in-vivo plasmin and thrombin activity favourably.

Adult↗
PubMed1986

Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.

The cell mediated immune response was evaluated in vivo in 29 patients with clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19 the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus III or lymphadenopathy associated virus). In the whole group, and in seronegative patients (n = 17), there was an inverse relation between exposure to clotting factor and skin response. In seropositive patients (n = 12) no such association was apparent. This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Studies on haematocrit in peripheral arterial disease.

Haematocrit is often elevated in peripheral arterial disease, and is an important determinant of blood viscosity and of platelet behaviour. We have studied the relationships of haematocrit to claudication, smoking habit, calf blood flow, platelet aggregation in whole blood, and the late complications of aortic bifurcation grafts. In 31 claudicants, blood viscosity, haematocrit and fibrinogen levels were significantly higher compared to 50 controls (p less than 0.01). However this was largely explained by a higher prevalence in claudicants of cigarette-smoking, which is associated with increased blood viscosity, haematocrit and fibrinogen levels. In 8 stable claudicants with high-normal haematocrit (mean 0.50), venesection reduced haematocrit to low-normal levels (mean 0.44). Resting calf blood flow was unchanged: peak flow increased slightly (17%) but oxygen delivery (peak flow X haemoglobin concentration) was unchanged. Spontaneous platelet aggregation in whole blood was studied using a single platelet counting method: the increase in haematocrit in patients with claudication was not associated with a significant increase in aggregation, and a negative association of haematocrit and aggregation was observed. In a preliminary retrospective study of patients with late complications of aortic bifurcation grafts, significantly higher haematocrits prior to operative were found compared to controls who had not returned to the clinic. Further prospective studies are required to assess the significance of haematocrit in peripheral arterial disease, and to determine whether any adverse effects are due to associations with smoking, rheology or platelet behaviour.

Adult↗
PubMed1986

A critical investigation into the existence of circulating platelet aggregates.

By a method of counting single platelets in diluted whole blood, platelet aggregates were quantified ex-vivo. Four groups: 20 thrombotic patients, 10 non-thrombotic patients, 10 healthy old controls and 10 healthy young controls were included in the study. Using a 19 gauge needle, with and without tubing, venous blood was taken into buffered EDTA, as a disaggregating agent and buffered EDTA-formalin, as the fixative. The amount of platelet aggregates quantified was affected by the quality of venepuncture or the rate of blood flow through the needle, but was unaffected by the presence of the tubing. There was no statistically significant difference between the four groups, in terms of the platelet aggregates quantified, but scanning electron microscopy revealed the presence of irreversible aggregates, composed of platelet red and white blood cells, in the blood of a greater number of thrombotic patients than non-thrombotic or healthy controls. Platelet aggregates were also quantified in aliquots of platelet rich plasma, and were found to be significantly greater than the corresponding values in whole blood. The difference appeared to be due to increased viscosity of the plasma, induced by the fixative which reduces platelet mobility during centrifugation. It is concluded that the platelet aggregates which disaggregate in buffered EDTA may represent an artifact of blood collection; the irreversible aggregates are suspected to represent the in vivo circulating aggregates.

Adult↗
PubMed1986

Blood viscosity as a factor in sensorineural hearing impairment.

The cause of sensorineural hearing impairment is unknown in a high proportion of patients. Since ischaemia is a possible factor, the relation between hearing threshold and blood viscosity, plasma viscosity, and haematocrit was investigated in 49 patients with idiopathic hearing loss, taking into account age, sex, smoking, and socioeconomic group. Hearing thresholds were unrelated to haematocrit or low-shear blood viscosity. Hearing impairment at high frequencies was directly related to high-shear blood viscosity and inversely related to plasma viscosity. The derived measure of red-cell rigidity was significantly related at all frequencies to hearing thresholds. A second study of 92 subjects from a population sample confirmed the inverse relation with plasma viscosity and lack of relation with haematocrit. Increased pure-tone thresholds appear to be related to increased red-cell rigidity; this may be an important factor in sensorineural hearing impairment with implications for diagnosis and prevention.

Adult↗