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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 109 records · Page 6Linked to original sources
PubMed1996

Hepatitis C virus in saliva of haemophiliac patients attending an oral surgery unit.

This study determined the frequency with which hepatitis C virus (HCV) could be detected in the saliva of 21 HCV-seropositive haemophiliac patients attending an Oral Surgery Unit. All sera were positive for HCV RNA by the polymerase chain reaction (PCR). Six of the patients were also HIV antibody positive. Saliva was collected both by spitting into a Universal container (whole saliva), and by means of Salivettes. Following RNA extraction from saliva specimens and synthesis of cDNA, nested PCR was performed. Amplified DNA was detected by agarose gel electrophoresis and ethidium bromide staining. Overall, HCV was detected in saliva from 10 of the subjects (8 HIV seronegative and 2 HIV seropositive) but there was not complete concordance between the Salivette specimens and normal whole saliva. Analysis of pellet and supernate fractions from whole saliva produced similar discrepancies. Repeat runs of PCR for HCV following freezing and thawing of the initially positive saliva specimens were unsuccessful. It was concluded that HCV is present in the saliva of some haemophiliac patients. However, careful optimisation of sample handling and storage methods and of PCR technique are required before the true prevalence of HCV shedding in saliva can be determined.

Adult↗
PubMed1996

Clinical, biochemical, and rheologic factors affecting the outcome of infrainguinal bypass grafting.

PURPOSE: The purpose of this study was to determine the effects of patient characteristics, blood rheology, and plasma biochemistry on the outcome of infrainguinal bypass grafting. METHODS: Blood rheology, plasma fibrinogen, cross-linked fibrin degradation products, von Willebrand factor (vWf) and other endothelial products, and clinical variables including smoking markers were determined before surgery in patients with 184 consecutive infrainguinal bypass grafts (90 vein, 94 synthetic grafts). RESULTS: Fifty (27%) graft occlusions and 17 (9%) deaths occurred within 1 year of surgery. On univariate analysis a poor outcome was associated with elevated preoperative plasma fibrinogen, fibrin degradation products, vWf, and platelet levels, reduced hemoglobin and systolic ankle pressure, a below-knee anastomosis, a decrease in patent calf vessels, and the presence of tissue necrosis (all p < 0.001). On multivariate analysis increased preoperative vWf levels were predictive of poor postoperative outcome (relative hazard for upper quartile versus lower quartile = 1.82), as were a low systolic ankle pressure (relative hazard = 2.51), presence of tissue necrosis (relative hazard = 2.73), and female sex (relative hazard = 1.9). None of the other variables studied was related to outcome. With a preoperative risk score derived from the results, graft patency rates within 3 months of surgery fell to less than 25% with risk scores in the upper quartile. CONCLUSIONS: Preoperative measurement of plasma vWf may enable more accurate prediction of the outcome of infrainguinal revascularization and when combined with other variables could assist in patient selection for these procedures. The association of vWf with graft occlusion supports a role for endothelial disturbance in graft occlusion.

Adult↗
PubMed1996

Variation in cardiovascular risk factors by angiographic site of lower limb atherosclerosis.

OBJECTIVE: To determine differences in the levels of the cardiovascular risk factors, cigarette smoking, serum lipids and blood pressure, between three groups of patients with different sites of lower limb atherosclerosis. DESIGN: Cross-sectional survey of a consecutive series of patients with symptoms of either intermittent claudication or rest pain. METHODS AND MATERIALS: One hundred and ninety-two men and women who had undergone angiography were classified using the Bollinger scoring system into groups with predominantly aortoiliac, femoropopliteal or dual-site disease. History of cigarette smoking, serum cotinine, serum thiocyanate, total cholesterol and HDL cholesterol were estimated. Systolic and diastolic pressures were measured and the ankle brachial pressure index (ABPI) was calculated. RESULTS: Eighty-five patients were classified as having femoropopliteal disease, 34 aortoiliac disease and 73 dual-site disease. After adjusting for age, sex and severity of disease, aortoiliac patients were significantly younger (p </- 0.001), more likely to be female and current smokers, and had the highest levels of diastolic blood pressure. Life time cigarette consumption (pack-years) and total cholesterol concentrations were highest in femoropopliteal disease. Patients with dual-site disease were more likely to have had a myocardial infarction and angina pectoris (p </- 0.05). Systolic blood pressure was also highest in this group. CONCLUSION: different levels of cardiovascular risk factors may predispose individuals to atherosclerosis at different sites in the lower limb. Large population studies would be required to delineate the risks more precisely.

Adult↗
PubMed1996

Warfarin and aspirin as thromboprophylaxis in atrial fibrillation.

1. Anticoagulant therapy with warfarin is now established as effective thromboprophylaxis against stroke in atrial fibrillation, in high-risk persons. Aspirin is indicated in moderate-risk persons or if warfarin is contraindicated. 2. Risk stratification is suggested, using clinical factors supplemented by echocardiography, to aid choice of prophylaxis. 3. Further studies are required to establish how best to identify undiagnosed patients who have atrial fibrillation; to develop new therapeutic strategies; and to refine risk stratification to define which patients with atrial fibrillation are at the highest risk of stroke.

Anticoagulants↗
PubMed1996

Haemostatic and rheological factors in intermittent claudication: the influence of smoking and extent of arterial disease.

Patients with intermittent claudication have been reported to have disturbances in blood rheology and haemostasis. Whether these disturbances are a result of, or largely independent of, smoking history and arterial narrowing has not yet been established. The levels of whole blood and plasma viscosity, haematocrit, von Willebrand factor antigen, fibrin D-dimer antigen and urinary fibrinopeptide A antigen were compared in 617 claudicants and 722 controls from two epidemiological studies in Edinburgh. After adjustment for age and sex, all factors, except whole blood viscosity and haematocrit, were significantly higher in the claudicants compared to controls (P < or = 0.001). The risk of intermittent claudication was significantly raised for unit change in each factor, except for whole blood viscosity and haematocrit. Adjustment for lifetime smoking had little effect on the odds ratios. After further adjustment for the ankle brachial pressure index (as a measure of the extent of peripheral arterial disease), haematocrit, von Willebrand factor and urinary fibrinopeptide A showed a significant independent relationship with the risk of intermittent claudication. We conclude that the association between selected rheological and haemostatic factors and leg ischaemia is largely independent of both smoking history and the extent of arterial narrowing, and may be directly related to microvascular ischaemia.

Aged↗
PubMed1996

Haemostatic factors, atherosclerosis and risk of abdominal aortic aneurysm.

Abdominal aortic aneurysms have traditionally been thought to be a consequence of severe atherosclerosis of the arterial wall. To date, the role of haemostatic factors in aneurysmal disease has not been extensively researched. The aim of this study was to see if such factors were independently related to the occurrence of aortic aneurysm. Furthermore, were the associations maintained after taking into account the presence of underlying atherosclerotic disease? Using data from the Edinburgh Artery Study, a nested case-control design was used involving 40 cases of aortic aneurysm, each being matched to five controls by sex and within a 5-year age band. After adjustment for age and sex, both fibrinogen (P < or = 0.01) and fibrin D-dimer (P < or = 0.001) were each associated with a significant increased risk of aneurysm. Further adjustment for packyears, history of cardiovascular disease and the ankle brachial pressure index resulted in odds ratios of 1.51 (95% CI 1.05 to 2.16, P < or = 0.05) for fibrinogen and 3.75 (95% CI 1.80 to 7.82, P < or = 0.001) for fibrin D-dimer. These associations probably arise as a consequence of fibrin deposition and turnover within the aneurysmal sac, although further prospective studies are needed before thrombotic factors can be used in the identification of a group who are at high risk of developing an abdominal aortic aneurysm.

Aged↗
PubMed1996

Blood viscosity, coagulation, and activated protein C resistance in central retinal vein occlusion: a population controlled study.

BACKGROUND: The role of blood viscosity and haemostasis has been investigated in mixed groups of patients with branch and central retinal vein occlusion (CRVO) with conflicting results. This may have partly been due to the different aetiologies of these two types of vein occlusion. METHODS: In this study viscosity and coagulation (including activated protein C resistance) were examined in 87 patients with CRVO and compared with the results from an age-matched, population based control group. RESULTS: Viscosity variables were higher in CRVO than in controls which suggested that reduced red cell deformability was associated with the occurrence of CRVO. A higher percentage of the patients with CRVO (12%) had activated protein C resistance than controls (5%). Patients who developed the complication of iris neovascularisation had relatively low antithrombin III, factor VII, and tissue plasminogen activator indicating both a tendency to thrombus formation and a reduction in fibrinolytic activity. CONCLUSION: Increased blood viscosity may contribute to the production of CRVO by inducing stasis of blood flow, with thrombus formation in at risk individuals who go on to develop iris neovascularisation.

Adult↗
PubMed1996

Thrombogenesis in mitral regurgitation and aortic stenosis.

The exact mechanisms for thrombus formation in patients with valvular heart disease have not been clearly defined. Abnormalities in plasma coagulation factors indicative of a prothrombotic state may in part account for the risk of stroke and thromboembolism in such patients. The aim of this study was, therefore, to determine the effects of mitral regurgitation (MR) and aortic stenosis (AS) on plasma fibrinogen or fibrin D-dimer levels as indices of a thrombogenic (or prothrombotic) state. A total of 25 patients with valve disease in sinus rhythm were studied: 12 patients (all women; mean age fifty-five years, sem 3.3) with MR; and 13 patients (7 men, 6 women; mean age fifty-seven years, sem 3.5) with AS were studied. Patients with MR had a median plasma fibrinogen that was significantly elevated when compared with female population values (median difference 0.62 g/L; 95% confidence intervals (CI) 0.27 to 1.05, P = 0.0016). However, these patients had a median plasma fibrin D-dimer that was lower than that for population controls (median difference 21 ng/mL; 95% CI 0 to 38, P = 0.05). Patients with aortic valve disease had a median plasma fibrinogen that was significantly increased when compared with population controls (median difference 0.82 g/L; 95% CI 0.34 to 1.24, P = 0.001). These patients had a plasma fibrin D-dimer level that was similar to population values (median difference 3 ng/mL; 95% CI -25 to 22, P = 0.80). Patients with MR or AS have higher plasma fibrinogen levels when compared with "normal" population values, suggesting possible hemorheologic abnormalities in these patients. Subjects with MR had lower plasma fibrin D-dimer levels, suggesting lesser intravascular clotting, consistent with clinical echocardiographic studies. Subjects with AS had plasma fibrin D-dimer levels similar to the "normal" population values, suggestive of a different pathophysiological mechanism for thromboembolism. These findings add to an improved understanding of the relationship between clinical observations and the significance of plasma fibrinogen and fibrin D-dimer levels in thrombogenesis.

Aortic Valve Stenosis↗
PubMed1996

Management of suspected acute venous thromboembolism in a general and maternity hospital.

A retrospective study of the management of patients with suspected acute deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) in a general and maternity hospital was conducted over a two month period in 1992. Ninety six patients with suspected DVT/PTE were identified, of whom only two were pregnant. Forty four patients had suspected DVT and confirmatory investigations were performed in 84%. The most common risk factor for DVT was intra-venous drug (IVD) use. Unfractionated heparin was prescribed to all patients except one with acute DVT at an average daily dose of 25,000 iu. In patients receiving heparin, 68% had measurements of the activated partial thromboplastin time (APTT) ratio and on 38% of occasions the result was subtherapeutic. Complications of heparin therapy were infrequent. Fifty two patients had suspected PTE and 50 underwent ventilation/perfusion (V/Q) scanning. No patient underwent pulmonary angiography. The management of patients with normal, low and high probability V/Q scans was in keeping with the guidelines, but only 8% [corrected] of patients with an intermediate V/Q scan result had further investigations and 33% received heparin. This study revealed suboptimal anticoagulation of patients with acute DVT and scope for improvement in the management of patients with an intermediate V/Q scan result.

Acute Disease↗
PubMed1996

The influence of biomaterials on inflammatory responses to cardiopulmonary bypass.

The nature of cardiopulmonary bypass and the complexity of the inflammatory response make the detection and interpretation of a biomaterial influence difficult. However, if mediation of the inflammatory response is considered to be an appropriate clinical goal, alteration to the biomaterial influence merits further investigation.

Biocompatible Materials↗
PubMed1996

Smoking, haemostatic factors and the severity of aorto-iliac and femoro-popliteal disease.

To determine relationships between haemostatic and rheological factors and severity of peripheral atherosclerosis and differences by site, an angiographic cross-sectional survey was carried out on 192 men and women with intermittent claudication or rest pain. 34 patients were classified as having aorto-iliac disease, 85 femoro-popliteal disease and 73 dual-site disease. Mean levels of haemostatic or rheological factors did not differ significantly between the three site groups. In all 192 patients, disease severity in the femoro-popliteal segments was correlated with plasma nephelometric fibrinogen (r = 0.20, p < or = 0.01), von Willebrand factor (r = 0.14, p < or = 0.05) and fibrin D-dimer (r = 0.22, p < or = 0.001). On multiple regression analyses, fibrinogen was independently associated with disease severity in the femoro-popliteal segments (p < or = 0.05), but not in the aorto-iliac segments. Adjustment for packyears or serum thiocyanate had little effect on the association of fibrinogen with severity of disease. An inverse relationship between plasminogen activator inhibitor and disease severity in the femoro-popliteal segments was found only in men (r = 0.24, p < or = 0.01). We conclude that elevated fibrinogen and disturbed fibrinolytic activity may be related to the extent of disease within the femoro-popliteal arteries, more so than in the aorto-iliac arteries.

Adult↗
PubMed1996

High purity factor IX and prothrombin complex concentrate (PCC): pharmacokinetics and evidence that factor IXa is the thrombogenic trigger in PCC.

Recent studies using assays for surrogate markers of thrombogenicity in man have demonstrated that activation of the coagulation system occurs following infusion of clinical doses of prothrombin complex concentrates (PCC) but not after the same doses of high-purity factor IX concentrates (HP-FIX) in patients with haemophilia B. Here we have investigated the mechanism of such thrombogenesis by applying assays that detect early-through to late-events in coagulation system activation in a pharmacokinetic cross-over study of 50 IU/kg PCC and a new HP-FIX product in haemophilia B patients. Satisfactory recoveries and half-lives were observed for both concentrates. HP-FIX caused no increases in thrombin-antithrombin III complex (TAT), prothrombin activation peptide fragment F1+2 (F1+2), factor X activation peptide (FXAP) or factor VIIa (FVIIa). In contrast the same dose of factor IX in the form of PCC was followed by significant increases over pre-infusion levels of TAT, F1+2 and FXAP, but not FVIIa. Elevations of FIXAP occurred after both HP-FIX and PCC but did not reach normal levels and were attributed to normalisation of the FIX concentration in those patients whose levels of FIXAP were initially low. We conclude that the thrombogenic trigger associated with PCC infusion occurs at the level of factor X activation. In the absence of any increase in FVIIa, we would attribute this to the likely presence of FIXa in the PCC.

Adult↗
PubMed1996

Inter-relationships of plasma fibrinogen, low-density lipoprotein cholesterol, cigarette smoking and the prevalence of cardiovascular disease.

BACKGROUND: The magnitude of the cardiovascular risk associated with plasma fibrinogen concentration is influenced separately by cigarette smoking and by low-density lipoprotein (LDL) cholesterol levels. The effects of combinations of these factors on risk and the extent to which inclusion of the plasma fibrinogen level further refines the risks associated with smoking and high LDL cholesterol levels are not known. OBJECTIVE: To determine the inter-relationships among all of the three factors smoking, LDL cholesterol level and fibrinogen level with respect to the occurrence of cardiovascular disease. METHODS: The study was part of the Edinburgh Artery Study, which was a cross-sectional random sample survey of 1592 men and women aged 55-74 years. The assessment of cardiovascular disease included recall of diagnosis by a doctor of angina or myocardial infarction, intermittent claudication determined by a questionnaire and measurement of ankle systolic blood pressure. RESULTS: The odds ratio for disease in smokers in the top tertiles of plasma fibrinogen and LDL cholesterol levels was 7.7 (95% confidence interval 3.0-19.8; P < or = 0.001). Neither a multiplicative nor a synergistic effect of the three factors on the odds of disease was observed but the level of each contributed to the risk. For example, in current smokers in the bottom tertile of LDL cholesterol level, the odds of disease were 6.1 (95% confidence interval 2.2-17.0; P < or = 0.001) in the top tertile, 2.9 (95% confidence interval 1.0-8.6; P < or = 0.05) in the middle tertile and 1.6 (95% confidence interval 0.5-4.8; P > 0.05) in the bottom tertile of plasma fibrinogen level. Subjects in the bottom tertile of plasma fibrinogen level did not have significantly elevated (P < 0.05) risks irrespective of LDL cholesterol levels and smoking status. CONCLUSION: The incorporation of plasma fibrinogen level permitted more precise delineation of the odds of disease within categories of smoking and LDL cholesterol concentration. These relationships need to be investigated further in prospective studies.

Aged↗
PubMed1996

In vitro blood compatibility evaluation of hollow fibre membrane using a controlled flow system: a comparative study.

A procedure has been established for the in vitro assessment of hollow fibre haemodialysis membranes. A 30 ml syringe containing 20 ml of fresh non-anticoagulated blood was mounted onto a non-pulsatile syringe pump and blood was perfused through minimodules constructed from 80 fibres retrieved from Cuprophan (Baxter ST15), cellulose acetate (M57-12, JMS Co Ltd, Hiroshima, Japan), and AN69HF (Filtral 20, Hospal, France) dialysers. Samples were collected before perfusion, 3, 6, 9 and 12 minutes. The modules were clamped vertically to minimise the effect of red cell pooling and the dialysate compartment was filled with 0.9% saline to minimise ultrafiltration. After sample processing, complement C3a, thrombin-antithrombin III complexes, prothrombin F1 + 2, and factor XII-like activity were evaluated. The results indicated that the system could discriminate between the membranes evaluated and therefore was a relevant procedure for the assessment of hollow fibre haemodialysis membranes.

Antithrombin III↗
PubMed1995

Effects of warfarin therapy on plasma fibrinogen, von Willebrand factor, and fibrin D-dimer in left ventricular dysfunction secondary to coronary artery disease with and without aneurysms.

Cardiac impairment in patients is associated with intracardiac thrombus formation and thromboembolism. A high prothrombotic state may exist in such patients, and abnormalities in plasma markers of thrombogenesis may be indicative of such a state. The aim of this study was to determine the associations of left ventricular (LV) aneurysm formation and dysfunction with plasma fibrinogen, von Willebrand factor, and fibrin D-dimer, which are markers associated with thrombus formation (thrombogenesis) and to investigate the effects of warfarin given to patients with LV aneurysms on fibrinogen and D-dimer levels. A cross-sectional study of 112 patients with coronary artery disease was initially performed: 34 patients had normal LV function (group 1); 30 had LV dysfunction without aneurysm formation (group 2); 29 had LV aneurysms without anticoagulation (group 3a); and 19 patients had LV aneurysms with warfarin therapy (group 3b). Results were compared with 158 population controls from a random population sample. A longitudinal study of 10 patients given warfarin was also performed. In group 1, plasma fibrinogen (median difference 0.36 g/L; p = 0.0009) and von Willebrand factor (median difference 17 IU/dl; p = 0.04) were elevated, whereas plasma D-dimer levels (median difference 23.0 ng/ml; p = 0.001) were lower than those in population control subjects. There were no significant differences in plasma fibrinogen, von Willebrand factor, or D-dimer levels between groups 1 and 2. In group 3a, plasma fibrinogen was elevated when compared with group 1 (median difference 0.6 g/L; p = 0.0001), with a trend toward high von Willebrand factor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Is diastolic dysfunction associated with thrombogenesis? A study of circulating markers of a prothrombotic state in patients with coronary artery disease.

Clinical data on the contributory role of heart failure to thromboembolic risk does not differentiate between systolic and diastolic left ventricular dysfunction. We therefore conducted a population-controlled cross-sectional study to determine levels of plasma fibrinogen (associated with thromboembolism), fibrin D-dimer (a marker of fibrin turnover) and von Willebrand factor (a marker of endothelial dysfunction) in patients with ischaemic heart disease (a common cause of diastolic dysfunction) in whom left ventricular diastolic function was defined by echocardiography. We studied 106 patients: those with normal left ventricular function (n = 42, Group 1); those with left ventricular dysfunction but without aneurysms (n = 34, Group 2); and those with left ventricular aneurysm formation (n = 30, Group 3). Each of these groups was subdivided into those with (a) and without (b) diastolic dysfunction. Diastolic dysfunction was present in over 60% of patients, irrespective of left ventricular systolic impairment. There were no significant differences in median levels of plasma fibrinogen, fibrin D-dimer or von Willebrand factor in each group of patients with ischaemic heart disease, whether or not left ventricular diastolic dysfunction was present (Mann-Whitney test; P = N.S.). Systolic (rather than diastolic) dysfunction was the main correlate of these (analysis of variance, general linear model--ANOVA-GLM--P < 0.05) and the greatest abnormalities of fibrinogen, endothelial dysfunction and intravascular fibrin turnover were seen in patients with left ventricular aneurysms whether or not diastolic dysfunction was present. This study demonstrates that there is no evidence of a significant additional contribution to thrombotic risk (as assessed by plasma fibrinogen, von Willebrand factor and fibrin D-dimer) for patients with left ventricular diastolic dysfunction. A relationship is noted between some prothrombotic factors and Doppler indices of flow, which suggests a possible association between cardiac haemodynamics and thrombogenesis.

Analysis of Variance↗
PubMed1995

Detection of mutations in ectopic factor VIII transcripts from nine haemophilia A patients and the correlation with phenotype.

Haemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of reverse transcription/polymerase chain reaction (RT-PCR) of ectopic factor VIII transcripts and PCR of genomic DNA to amplify the entire essential sequence of the factor VIII gene. Chemical mismatch cleavage analysis and direct sequencing have then be employed in order to facilitate a comprehensive search for mutations. In this report, we describe the characterisation of nine potentially pathogenic mutations, six of which are novel. The mutations include six single base substitutions (five missense, viz. D56E, V162M, G701D, A1834T and R1869I, and one nonsense, viz. R-5X), a single base deletion (5697delC), a gross deletion of exon 16 and one mRNA abnormality characteristic of the common intron-22-embedded F8A-mediated DNA inversion. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations, we have analysed them for evolutionary sequence conservation and for their involvement with sequence motifs catalogued in the PROSITE database of protein sites and patterns. Analysis of the sequences in the immediate vicinity of the mutations has revealed sequence features that may have had a possible role in mutagenesis.

Amino Acid Sequence↗