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Biomedical subjects

J F Burman

Publications and source records attributed to J F Burman.

At least 19 recordsLinked to original sources
PubMed2005

Thrombophilia in children with cystic fibrosis.

In some children with cystic fibrosis (CF), percutaneous long lines occlude sooner than expected (due to thrombophlebitis or thrombosis), and many have a totally implantable venous access device (TIVAD), a recognized complication of which is thrombosis. This complication is more likely if the child has an underlying thrombotic tendency, which may be enhanced in the presence of inflammatory lung disease. There are no reports of an identified association of heritable thrombophilia with CF, although individual cases have been recognized. Our aim was to determine the incidence of thrombophilia in children with CF. In a tertiary pediatric CF center, blood was screened for thrombophilia at annual review, and retested if abnormal. A thrombotic abnormality was found in 41/204 (20%) patients. These included activated protein C resistance (10/204, 5%) with a prevalence similar to that expected, but the following abnormalities had an increased prevalence: antithrombin deficiency (2/204, 1%), protein S deficiency (11/204, 5%), protein C deficiency (8/204, 4%), and lupus anticoagulant (18/204, 9%). There were no differences found in those with thrombophilia for the following parameters: age, gender, genotype, lung function, presence of Pseudomonas aeruginosa, prothrombin time, serum IgE, aspergillus-specific IgE, liver function, and blood inflammatory markers. Fifteen children had TIVADs, 4 of whom had evidence of thrombophilia. In conclusion, a significant proportion of patients had a thrombophilic abnormality. We recommend that thrombophilia screening be performed prior to insertion of a TIVAD, and also in those with a history of venous thrombosis, blocked TIVADs, or recurring problems with long lines.

Activated Protein C Resistance↗
PubMed2004

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia.

BACKGROUND: Coronary ischaemic syndromes are associated with neutrophil activation. The Bayer automated haematology analysers can detect increased light scatter of neutrophil populations, which correlates with neutrophil activation. We aimed to assess the role of an automated analyser in detecting systemic neutrophil activation in peripheral blood samples of patients with coronary ischaemia. METHODS: A prospective cross-sectional study was undertaken in 18 patients with chronic stable angina, 9 with unstable angina and 26 normal control subjects. Whole blood samples were taken to assess neutrophil count and light scatter, and serum samples were taken from some patients for assessment of Troponin T, C-reactive protein (CRP) and myeloperoxidase (MPO). In addition, whole blood was stimulated in vitro with interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine (fMLP) to assess changes in neutrophil light scatter detected by the analyser. RESULTS: Neutrophil light scatter was increased in patients with chronic stable and unstable angina compared to normal control subjects (normal subjects 74.1 (73.3, 75.0) (mean arbitrary units (95% confidence intervals, (CI)) vs. 78.6 (76.9, 80.3) in the chronic stable angina group P<0.001 and 77.1 (75.3, 79.0) in the unstable angina group P<0.007). In vitro stimulation of whole blood produced comparable increases in neutrophil light scatter when morphological changes in neutrophils were demonstrable under electron microscopy. CONCLUSIONS: Automated measurement of neutrophil activation by light scatter is possible using the Advia 120 analyser and is superior to a neutrophil count in discriminating groups with angina. This technique may be useful in monitoring disease activity and progression in coronary artery disease and in guiding the use of anti-inflammatory therapies.

Adult↗
PubMed2003

Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery.

A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery.

Adenosine Diphosphate↗
PubMed2002

Study of five cell salvage machines in coronary artery surgery.

We evaluated the effectiveness, ease of use and safety of five machines for blood salvage during coronary artery surgery. All were equally effective in concentrating red cells. We measured haemoglobin, packed cell volume, free haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d-dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed cell suspensions and in a unit of bank blood prepared for each patient. All machines were equally safe and easy to use and were equally effective in removing heparin and the physiological components measured. There were no adverse effects on patients. Clotting factors are severely depleted both in salvaged blood, even before washing, and in bank blood. Cell savers are a valuable adjunct to coronary artery surgery, but careful monitoring of coagulation is required when the volumes of either bank blood or salvaged blood are large.

Adult↗
PubMed2002

Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice.

BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular-weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty.

Adult↗
PubMed2001

High molecular weight kininogen deficiency: a patient who underwent cardiac surgery.

A 66 year old male, referred for cardiac surgery, was found to have high molecular weight kininogen deficiency (activity <1%). Apart from activated partial thromboplastin time (APTT) >300 s, tests of haemostasis were otherwise normal (factors VIII, IX, XI, XII and prekallikrein). No inhibitor of coagulation was found. The activated coagulation time (ACT) was 800 s pre-operatively and >1000 s after heparin. Heparin levels were measured directly by an anti-Xa chromogenic assay, with values of between 2.9 and 3.2 u/ml during cardiopulmonary bypass. Thrombin-antithrombin levels rose from 2.3*g/l before surgery to a peak of 83.5*g/l at the end of cardiopulmonary bypass. Cross linked fibrin d-dimers (XDP) levels rose from 100 ng/ml before operation to 600 ng/ml after protamine administration. The patient had no excess bleeding and no thrombotic complications from surgery. This patient shows that high molecular weight kininogen is not required for thrombin formation or fibrinolysis during cardiac surgery and illustrates the need to measure heparin directly in patients with such contact factor deficiencies.

Aged↗
PubMed2000

Diurnal variation in platelet aggregation iwth the PFA-100 platelet function analyser.

BACKGROUND: Myocardial infarction is commoner in the morning, and previous small studies suggesting diurnal variation in platelet aggregation have been limited to optical aggregometry with platelet-rich plasma and low shear. This phenomenon was studied using whole blood at high shear rates. METHOD: Fifteen healthy volunteers were venesected at 0800 hrs supine in bed immediately before rising, at 0830 hrs 30 min after rising, at 1200 hrs and 1700 hrs. Samples underwent the high shear method of PFA-100 using additional chemical agonists of collagen with ADP or collagen with epinephrine. PFA-100 results are reported as closure time of the experimental aperture in seconds, a longer time indicating less platelet aggregation. RESULTS: With both epinephrine and ADP, a non-significant shortening of closure time was seen on rising. Subsequently, with both agonists the closure time lengthened through the day. With ADP the difference was small (medians 0830 hrs: 85 s, 1700 hrs: 87.5 s) but statistically significant (p = 0.03). With epinephrine it was much more marked (medians 0830 hrs: 114.3 s, 1700 hrs: 140.5 s) and highly significant (p = 0.002). CONCLUSIONS: These findings demonstrate a diurnal rhythm in platelet function using whole blood at high shear rates. This is likely to be more applicable to the in vivo situation than previously reported optical aggregometry studies.

Adult↗
PubMed2000

Automated quantitation of circulating neutrophil and eosinophil activation in asthmatic patients.

BACKGROUND: Asthma has been associated with eosinophil activation, measured in serum, sputum, bronchoalveolar lavage (BAL) fluid, and urine. A whole blood automated method was developed to assess eosinophil and neutrophil activity in terms of peroxidase content and cell morphology using the Bayer haematology analyser. The method was applied to an in vitro stimulation model when fMLP was added to whole blood and the samples were then analysed for changes in granularity and shape. In addition, cells stimulated with interleukin (IL)-8 were examined by electron microscopy. METHODS: A cross sectional analysis was performed on venous blood from non-atopic, non-asthmatic normal subjects (n = 37), mild (n = 46) and symptomatic (n = 22) asthmatic patients on inhaled beta(2) agonist only, and more severe asthmatic patients (n = 17) on inhaled and oral corticosteroid therapy. Samples were analysed by the haematology analyser and peroxidase leucograms gated using the WinMDI software program. RESULTS: There were significant differences in the amount of light scatter by the neutrophil populations in the symptomatic (p = 0.007) and severe asthmatic (p = 0.0001) groups compared with the control group. However, abnormalities in eosinophil populations were not observed. In vitro activation of whole blood with fMLP caused similar changes in neutrophil light scatter, suggesting that neutrophil activation is present in peripheral blood of symptomatic asthmatic patients. IL-8 caused a change in shape of the neutrophils seen using transmission electron microscopy. CONCLUSIONS: Evidence of neutrophil activation can be seen in whole blood from patients with asthma using a novel automated method. This may potentially be applied to other inflammatory diseases.

Adult↗
PubMed2000

Tissue factor is rapidly elevated in plasma collected from the pericardial cavity during cardiopulmonary bypass.

There is growing evidence that the tissue factor/factor VIIa pathway of coagulation is enhanced during cardiopulmonary bypass. Hitherto, available evidence has suggested that upregulated monocyte bound tissue factor is made available, either in the blood collected from the site of surgery or on circulating cells. However, cellular upregulation is slow, while generation of factor VIIa in blood collected from the pericardial cavity is rapid. We have therefore investigated the possibility of an alternative source of tissue factor, plasma (as opposed to cellular) tissue factor in blood samples taken from the central vein catheter (systemic circulation) and collected from the pericardial cavity during cardiopulmonary bypass. Six patients undergoing first time cardiopulmonary bypass grafting were studied. Tissue factor antigen was found to be rapidly elevated (by 15 min) in the pericardial plasma, approximately 5-fold above systemic levels (p <0.004). Similar elevations were found in markers of coagulation activation, factor VIIa antigen (p = 0.066), prothrombin fragment F(1+2) (p <0.003) and thrombin-antithrombin complex (p <0.03). To explore whether plasma tissue factor was (or had been) functionally active, factor VIIa was measured also with the soluble tissue factor functional assay after removal of heparin. Functional factor VIIa activity fell significantly in the systemic circulation, probably due to the heparin-induced increase (approximately 15-fold) in tissue factor pathway inhibitor (TFPI), but was elevated in pericardial blood compared with that taken from the central line catheter (p <0.006). These results demonstrate that both components of the activation complex for the extrinsic pathway of coagulation are rapidly generated in pericardial blood during bypass.

Aged↗
PubMed1999

Evaluation of angiographic contrast media and platelet function with impedance aggregometry and the PFA-100 'platelet function analyser'.

BACKGROUND: Angiographic contrast media are used in balloon angioplasty and may influence thrombotic complications of the procedure. We studied the effect of different media on platelet aggregation in whole blood using impedance aggregometry and the PFA-100 'platelet function analyser' (Dade, USA). METHODS: Venous blood samples from 18 healthy volunteers were split into four aliquots and mixed with 10% normal saline control, non-ionic medium (iohexol), low-molecular weight ionic medium (ioxaglate) and high-molecular weight ionic medium (diatrizoate). Samples were studied with impedance aggregometry and the PFA-100. RESULTS: All media caused significant inhibition of aggregation compared with control with both methods (P<0.001). Antiplatelet potency was greatest with diatrizoate, intermediate with ioxaglate and least with iohexol with both methods (P<0.01). Electron microscopy of the PFA-100 membrane demonstrated occlusion of the experimental aperture with platelet thrombus in the control. Inhibition of platelet thrombus was seen with all media, greatest with diatrizoate, intermediate with ioxaglate and least with iohexol. CONCLUSIONS: The media studied significantly inhibited platelet aggregation in vitro and potency was greater with ionic than non-ionic media. These methods use a combination of shear and chemical agonist with whole blood and may reproduce in vivo arterial conditions better than other techniques.

Journal Article↗
PubMed1999

Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration.

Several recent studies have proposed that coagulation is triggered during cardiopulmonary bypass surgery by extrinsic pathway activation involving factor VIIa generation, but the methodology was indirect. Therefore, 12 patients were studied during routine cardiac and cardiopulmonary bypass surgery. Samples were taken before, during, and after bypass from the perfusate, from the aorta (retrograde cardiac drainage), pericardium, and collected suction fluid originating from the whole operative field. These samples were analyzed by enzyme-linked immunosorbent assay for 2-chain factor VIIa, by prothrombin F1+2 assay, by thrombin-antithrombin (TAT) assay, and for heparin concentration. Factor VIIa, F1+2, and TAT levels in samples from the pericardium were greatly elevated (mean, 0.92 to 1.01, 227 to 334, and 399 to 526 microg/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 microg/L, respectively; P<0. 05 for all), whereas levels in suction fluid were less consistently high. Factor VIIa and both F1+2 and thrombin-antithrombin levels in samples from the aorta, pericardium, and suction fluid were significantly correlated (r=0.57, P<0.001, n=111; and r=0.51, P<0. 001, n=105, respectively), and all were inversely correlated with heparin levels (r>-0.35, P<0.001, n>92). There was no evidence of factor VIIa generation in the circuit during bypass surgery, and both F1+2 and thrombin-antithrombin levels rose only approximately 2-fold, probably because heparin levels were higher than they were in the pericardium (P<0.05). We concluded that appreciable activation of factor VII occurs on the pericardium and that this is associated with increased thrombin generation. Ineffective local heparinization may be partly responsible. These results suggest that pericardium-induced activation of factor VII should be the target of anticoagulant strategies during cardiopulmonary bypass surgery.

Aged↗
PubMed1994

Role of factor XII in thrombin generation and fibrinolysis during cardiopulmonary bypass.

During cardiopulmonary bypass, thrombin is generated, which is thought to be initiated by activation of factor XII on the surface of the bypass equipment. We present a patient with severe factor XII deficiency who underwent cardiac surgery. As much thrombin was formed during cardiopulmonary bypass (measured by the prothrombin activation fragment F1 + 2 and thrombin-antithrombin complexes) as in normal patients, showing that factor XII was not necessary for thrombin generation. Factor X, but not factor IX, was activated (as measured by their activation peptides), and this activation correlated with F1 + 2 and thrombin-antithrombin complexes, suggesting that the tissue-factor/factor-VIIa pathway is the trigger for thrombin formation.

Antithrombin III↗
PubMed1994

Review of blood transfusion practices in thoracic surgery.

Between September 1, 1989, and August 31, 1990, 516 patients were admitted to the Royal Brompton National Heart and Lung Hospital for thoracic operations. A prospective audit recorded the nature and extent of operation, the histologic diagnosis, and the number of units of blood prepared and transfused during hospitalization. Cross-matched blood was requested in 243 patients but only 16.1% of these received transfusion. In total, 1,295 units of whole blood or red cell concentrate were cross-matched and made immediately available in the operating suite at the time of operation. Only 322 units were administered (cross-match to transfusion ratio of 4.02:1). Almost half of the patients who received transfusions received 2 units or less, a third received 3 or 4 units, 10% between 5 and 10 units, and 8.4% required more than 10 units during their hospital stay. The nature and extent of resection was an indicator of the need for transfusion. Other important predisposing factors included a previous thoracic operation, resection for inflammatory disease, decortication of empyema thoracis, chest wall resection, or thoracoplasty. Other thoracic procedures such as pleurodesis, pleurectomy, open lung biopsy, pectus correction, operation for bullous lung disease, and mediastinoscopy had a negligible transfusion requirement. The data suggest that understanding risk factors for transfusion requirements of patients undergoing thoracic surgical procedures should optimize present resources. This is critical when exploiting the limited availability of donated blood and blood products. Similarly, anticipation of transfusion requirements takes best advantage of manpower within the blood bank and minimizes unnecessary and avoidable blood wastage and expenditure.

Blood Grouping and Crossmatching↗
PubMed1992

Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women.

Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.

Antithrombins↗
PubMed1986

Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues.

Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.

Aged↗