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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 181 records · Page 10Linked to original sources
PubMed1992

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Genetic variation at fibrinogen loci and plasma fibrinogen levels.

In view of the controversy regarding genetic variation at the fibrinogen loci and plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI), beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects whose plasma fibrinogen was determined by clotting and nephelometric assays. Strong linkage disequilibrium was found between the alpha/TaqI and gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known physical order of these loci and suggests a relative excess of recombination in the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay method, when corrected or uncorrected for age, sex, and smoking habit, did not show any statistically significant associations with the four fibrinogen polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either singly or when analysed as a haplotype.

Blotting, Southern↗
PubMed1992

Blood viscosity and retinopathy of prematurity: a preliminary report.

Whole blood viscosity (WBV) and haematocrit (Hct) were measured in 8 very low birth weight premature neonates developing acute severe retinopathy of prematurity (ROP) and 7 control neonates without retinopathy or mild ROP. Single samples were collected at 32-34 weeks conceptual age. There was no statistically significant difference in WBV or Hct between the two groups. The results of this preliminary report suggest that WBV does not appear to play a major role in the development of advanced ROP, though larger studies are required to investigate this further.

Blood Viscosity↗
PubMed1992

Patterns of blood response during cardiopulmonary bypass.

Monitoring of cardiopulmonary bypass (CPB) in terms of alterations to the concentrations of selected blood constituents leads to contrasting patterns of response. This has been verified by determining the influence of CPB on the activation of fibrinolysis, complement, leucocytes and the contact phase of coagulation. Fibrinolytic activity was determined by fibrin degradation products (X-FDP's), complement activation by C3a and C5a, leucocyte activation by granulocyte elastase and contact activation by factor XII-like activity (FXIIA). Five patients undergoing elective coronary artery surgery using a bubble oxygenator and pulsatile perfusion were studied. X-FDP's rose gradually during CPB and remained elevated. Similar patterns were observed for elastase and FXIIA. In contrast, C3a rose sharply with peak values at 1 1/2-2h of bypass while C5a did not show significant changes during bypass. The data obtained have enabled the establishment of response patterns for parameters in CPB which will provide information relevant to the clinical application of biomaterials.

Biocompatible Materials↗
PubMed1991

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina.

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.

Adult↗
PubMed1991

B cell dysfunction in haemophilia in the absence and presence of HIV-1 infection.

56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and an impaired response to pokeweed mitogen and Staph Aureus protein A. Implying a shift in the proportions of partially and fully activated B cells. In the absence of HIV-1 infection there was a shift to a greater proportion of partially activated B cells in patients with severe liver disease. The remainder had in vitro immunoglobulin production comparable to controls. B cell abnormalities occur early in the course of HIV-1 infection. Liver disease and not clotting factor concentrate treatment cause B cell abnormalities in the absence of HIV-1 infection in haemophilia.

Adolescent↗
PubMed1991

Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects.

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.

Acute Disease↗
PubMed1991

T cell sensitization to factor VIII in haemophilia A?

Previous studies have indicated that factor VIII concentrates have a direct inhibitory effect on the proliferation of peripheral blood mononuclear cells (PBMC) obtained from normal volunteers. We have studied the effects of an intermediate and high purity factor VIII concentrate on haemophiliac PBMC. Intermediate purity factor VIII concentrate inhibited PBMC proliferation, the high purity factor VIII concentrate had no effect. The high purity factor VIII concentrate increased production of the lymphokine interleukin 2, suggesting the presence of a clone of T cells sensitized to factor VIII.

Albumins↗
PubMed1991

Do rheological variables play a role in diabetic peripheral neuropathy?

Whole blood viscosity and its determinants were measured in diabetic patients with and without peripheral neuropathy to assess whether these variables could have a role in the microvascular aetiology of diabetic peripheral neuropathy. Although corrected whole blood viscosity at high and low shear rates (5.29 +/- 0.51 and 21.10 +/- 3.03 mPa s), plasma viscosity (1.41 +/- 0.13 mPa s), and red cell filtration ratio (0.49 +/- 0.04) in diabetic patients were significantly different from non-diabetic control subjects (high shear rate 4.83 +/- 0.54, low shear rate 17.36 +/- 2.78, plasma 1.29 +/- 0.09 mPa s, all p less than 0.001, and red cell filtration ratio 0.55 +/- 0.03, p less than 0.001) there were no significant differences between diabetic patients with neuropathy and those without. Blood rheology is altered to a similar extent in diabetic patients with and without neuropathy.

Blood Viscosity↗
PubMed1991

Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies.

OBJECTIVE: To review the obstetric and gynaecological problems in women with congenital coagulopathies. DESIGN: Retrospective review. SETTING: Regional Adult Haemophilia Unit, Glasgow Royal Infirmary. SUBJECTS: All women in contact with the Unit over a period of 30 years, comprising eight with von Willebrand's disease, 18 obligate carriers of haemophilia A and five obligate carriers of Christmas disease. Each woman was interviewed and details of their obstetric and gynaecological histories were obtained and their case records were reviewed. MAIN OUTCOME MEASURES: Haemostatic changes associated with pregnancy and gynaecological problems. RESULTS: In 14 pregnancies in seven patients with von Willebrand's disease, there were four primary and four secondary post-partum haemorrhages and a large perineal haematoma complicating an episiotomy. These problems arose despite the endogenous rise in factor VIIIc seen with pregnancy. All women seen with von Willebrand's disease complained of menorrhagia and had been referred to gynaecologists. Treatment included danazol, tranexamic acid and the contraceptive pill. Diagnostic curettage resulted in severe haemorrhage in one woman and two women with pelvic pain and dyspareunia were found to have spontaneous broad ligament haematomas, one requiring surgery. In 43 pregnancies in obligate carriers of haemophilia A and Christmas disease there were five post-partum haemorrhages and a large perineal haematoma. CONCLUSION: In von Willebrand's disease it should be noted that adequate laboratory correction of factor VIIIc levels does not ensure clinical haemostasis; hence platelet function should also be measured. Patients with congenital coagulopathies pose particular problems for the obstetrician and gynaecologist and should be managed in close association with the local haemophilia centre.

Blood Coagulation Disorders↗
PubMed1991

Early experience with intra-arterial thrombolytic therapy for peripheral arterial occlusion.

The authors present their early experience with local intra-arterial thrombolytic therapy for peripheral arterial occlusions causing limb threatening ischaemia, using streptokinase or urokinase. Ten patients were treated in a period of one year. Five patients had successful recanalisation, two patients had partial success and three patients required major amputation. The indications, contraindications and results of this treatment are reviewed.

Adult↗
PubMed1991

Modification of the influence of biomaterials on contact activation.

Knowledge of the influence of biomaterials on the contact phase activation of blood is important. Consequently, it is important to examine if the biomaterial influence is modified by the action of anticoagulants. Contact activation was determined by measuring FXII activity (FXIIA) by a chromogenic substrate assay. Cuprophan in the absence of anticoagulants and in the presence of heparin, low molecular weight heparin (LMWH) and hirudin was compared with controls. The controls were a polystyrene incubation test cell (PS) and two polyamide membranes, NR (zeta potential -28.6 mv and NRZ (zeta potential--18.0 mv). The investigation has confirmed that measurement of FXIIA is material dependent and demonstrated that contact activation can be mediated by antithrombotic agent.

Anticoagulants↗
PubMed1990

Haemostatic abnormalities and outcome in patients with operable breast cancer.

The predictive value for cancer recurrence of five measurements of haemostatic activity was studied in 89 patients with operable breast cancer. Neither preoperative nor sequential measurements up to 9 months postoperatively of fibrinopeptide A, fibrin fragment B beta 15-42, fibrinogen and serum fibrin(ogen) degradation products nor the fibrin plate lysis assay correlated with early recurrent disease. B beta 15-42 values were higher preoperatively in patients with oestrogen receptor positive tumours (P = 0.017). Mean B beta 15-42 values rose postoperatively (P = 0.003), largely because of an increase in patients with oestrogen receptor negative tumours.

Adult↗
PubMed1990

Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study.

Plasma fibrinogen was measured in a sample of 8824 men and women aged 40-59 years participating in the Scottish Heart Health Study, and related to cardiovascular risk factors. Women had higher fibrinogen levels than men. In both sexes, multivariate analysis showed that fibrinogen was positively associated with age, smoking, total cholesterol and body mass index and negatively associated with alcohol consumption. Among women, early menopause and systolic blood pressure were also associated with fibrinogen levels. Univariate analyses showed weak positive associations with fish consumption for both sexes although only male white fish consumption entered the final model. Women with a history of contraceptive pill usage had significantly lower fibrinogen levels. The relationship between fibrinogen and physical activity was complex, and could largely be explained by smoking. These findings support the hypothesis that raised fibrinogen is one mechanism by which several major risk factors may promote coronary heart disease. However, known risk factors explained, at most, 10% of the total variance in fibrinogen levels among the general population.

Adult↗
PubMed1990

Stable angina pectoris and controlled ischemia: what causes the abnormalities in whole blood filterability?

The determinants of the altered whole blood filterability observed during coronary ischemia are still under discussion. Since no studies have been carried out to date on what exactly causes these alterations during the early stages of controlled ischemia in coronary heart disease, a model was set up using a bicycle ergometer test (with a 25 W increase every 2 minutes). Blood samples were taken from 48 stable angina pectoris patients and from a group of 28 matched controls before and immediately after exercise and 8 minutes later. Plasma viscosity, the filterability (through 5 microns diameter pore filters) of whole blood, erythrocytes, and polymorphonuclear and mononuclear leukocytes (separated by density gradient) were monitored. Alterations in whole blood filterability could be linked only to an impairment in polymorphonuclear cell filterability in those stable angina pectoris patients who reported chest pain and/or whose ST segment depression was greater than or equal to 2 mm.

Angina Pectoris↗