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Biomedical subjects

D Bareford

Publications and source records attributed to D Bareford.

At least 37 records · Page 2Linked to original sources

Vitamin E correlates inversely with non-transferrin-bound iron in sickle cell disease.

Decreased serum vitamin E levels are found in homozygous sickle cell disease (SCD). Excessive transfusions may lead high non-transferrin-bound iron (NTBI). Hypothesizing a relationship between the two, vitamin E (measured using high performance liquid chromatography) was significantly lower in 30 SCD patients than in 30 age-/sex-matched controls (P < 0.001), but NTBI (bleomycin assay) was higher (P < 0.001). Vitamin E was lower in 10 transfused patients than in 20 non-transfused patients (P < 0.001) with a significant inverse correlation between the NTBI and vitamin E (r = -0.58, P < 0.001). NTBI associated with iron overload in SCD may increase the potential for oxidative damage and low vitamin E activity may compound this effect.

Adult↗

A single (investigator)-blind randomised control trial comparing the effects of quinapril and nifedipine on platelet function in patients with mild to moderate hypertension.

The effect of quinapril and nifedipine on platelet aggregation, vascular endothelial function and coagulation system activity, was compared in a parallel-group, investigator-blind study carried out on patients with mild to moderate hypertension but no other diseases or receiving medication which might affect platelet function, vascular endothelium or coagulation. Forty patients (two groups of 20 patients each) and 20 control subjects were recruited. Patients were randomised to receive either quinapril or nifedipine retard and the dose escalated to control hypertension. Platelet aggregation studies were assessed serially and beta-thromboglobulin, angiotensin-converting enzyme (ACE), von Willebrand factor (vWF) coagulation factors VIIIc, XII and fibrinogen were measured at the beginning and end of the 12-week period. Blood pressure was adequately controlled in all patients in both groups. Platelet function was impaired in certain parameters (slope of the reaction with ADP and collagen and maximum aggregation with collagen) in the patient group compared to controls before treatment and this improved in patients on quinapril but not on nifedipine; likewise beta-thromboglobulin was higher in the patient group and fell significantly in the quinapril group but not those on nifedipine. Measurements of endothelial function and coagulation were normal before treatment and showed no alteration during the study, except in the expected fall in plasma ACE in the quinapril group. The results indicate that the ACE inhibitor, quinapril, has a beneficial effect on platelet function unlike the calcium channel blocker, nifedipine.

Adult↗

Increased soluble P-selectin in patients with haematological and breast cancer: a comparison with fibrinogen, plasminogen activator inhibitor and von Willebrand factor.

Abnormal platelet activation and an increased risk of thrombosis are frequent findings in cancer. As soluble adhesion molecule P-selectin is being increasingly recognized as reflecting increased platelet activation, we hypothesized raised levels in patients with cancer, obtaining plasma from 24 patients with a cross-section of haematological cancers, 41 with breast cancer, and from an equal number of healthy controls for each patient group. Levels of soluble P-selectin were compared with those of von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity, fibrinolysis and coagulation, respectively). We found raised soluble P-selectin, fibrinogen and vWf in both patient groups compared with their controls (P < 0.01). vWf and soluble P-selectin were higher in the haematological cancers than in breast cancer patients (by 30 and 74%, respectively; both P < 0.01). There was no significant difference in levels of PAI-1 between any group. There were no differences in soluble P-selectin or vWf when the data from the women with breast cancer were classified according to tumour size, lymph node involvement or presence of vascular invasion. We conclude that the platelet marker soluble P-selectin is raised in both haematological and breast cancer, and is higher in the former, but is unrelated to the type or stage of breast cancer.

Adult↗

Chronic myeloid leukaemia occurring in a patient with hairy cell leukaemia.

Occurrences of second malignancies in hairy cell leukaemia are well recognised. Most of these malignancies are either solid tumours or lymphoproliferative disorders. The association of myeloproliferative disorders with hairy cell leukaemia (HCL) is very rare. This report describes a case of a patient with HCL who after remaining in remission developed Philadelphia chromosome positive chronic myeloid leukaemia (CML), which rapidly transformed to acute lymphoblastic leukaemia with further cytogenetic abnormalities.

Fatal Outcome↗

Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0.

Warfarin is a commonly used prophylactic agent for the prevention of thromboembolic disease. We hypothesized that racial background influenced warfarin dosage, and tested this by recording the international normalized ratio (INR) in 867 patients aged 40-90 routinely passing through our Anticoagulation Service whose target INR was 2-3. Mean (95% confidence interval) dose was 4.1 (4.0-4.2) mg/d in 737 Caucasians, 5.5 (4.9-6.1) mg/d in 72 Asians, and 6.7 (5. 8-7.6) mg/d in 58 Afro-Caribbeans (P < 0.05) between each group). In a subgroup of 302 (41 Asians, 22 Afro-Caribbeans, 239 Caucasians), body mass index did not influence warfarin use. Despite small numbers, we conclude that racial background, but not body mass index, is a determinant of warfarin dosage. The reasons for this could be genetic, cultural (diet related), or both.

Anticoagulants↗

Red cell exchange in sickle cell disease.

Red cell exchange transfusion is frequently of use in the management of patients with sickle cell disease either electively or therapeutically. Modern cell separators allow this procedure to be performed rapidly, effectively and safely. These machines have a number of advantages over manual exchange procedures. The patient remains isovolaemic, there is little loss of plasma or platelets, the procedure is relatively short and in elective circumstances can be performed on an outpatient basis. In this series 66 exchanges were performed on 21 patients with an overall increase in HbA of 70%. The COBE Spectra gave a mean increase in HbA of 77%, with the majority of patients achieving an HbA of > 90% post exchange. Automated redcell exchange was well tolerated by most patients, and adverse effects were limited to symptoms of hypocalcaemia which were easily treated, and to transfusion reactions. Cell separators can therefore be recommended for exchange transfusion in patients with sickle cell disease, who require an increase in HbA levels either prophylactically or therapeutically. They are safe, effective, easy and quick to use.

Anemia, Sickle Cell↗

Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation. Effects of introducing ultra-low-dose warfarin and aspirin.

BACKGROUND: Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin. (300 mg) therapy on thrombogenesis and platelet activation in AF. METHODS AND RESULTS: We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P < .001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P = .025) and a sequential reduction in median D-dimer levels at 2 (P = .001) and 6 (P < .001) weeks compared with baseline levels. CONCLUSIONS: Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.

Aged↗

Role of non-transferrin bound iron in iron overload and liver dysfunction in long term survivors of acute leukaemia and bone marrow transplantation.

AIMS: To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. METHODS: Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. RESULTS: Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. CONCLUSION: Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.

Adult↗

Predictors of ratio of placental weight to fetal weight in multiethnic community.

OBJECTIVE: To determine whether placental ratio is influenced by maternal ethnic origin, obesity, hypertension, and haematological indices of iron deficiency anaemia. DESIGN: Observational study. SETTING: District general hospital in Birmingham. SUBJECTS: 692 healthy nulliparous pregnant women, of whom 367 were European, 213 Asian, 99 Afro-Caribbean, and 13 of other or undocumented ethnic origin. MAIN OUTCOME MEASURES: Placental ratio and maternal body mass index, blood pressure, and haematological indices. RESULTS: Though birth weight and placental weight were lower in Asian women than in other groups, mean placental ratio was similar in Asian (19.5% (SD 3.3%)), European (20.0% (4.0%)), and Afro-Caribbean women (20.4% (5.3%)). Gestational age at birth was the main predictor of placental ratio in the univariate analysis (r = -0.34, P < 0.001) and multivariate analysis. The only other significant predictor of placental ratio in multivariate analysis was maternal body mass index, which was positively associated with placental ratio (r = 0.1, P = 0.01). Mean (SD) placental ratio was not significantly higher in women who developed gestational hypertension (20.4% (4.5%)) and pre-eclampsia (23.3% (7.3%)) than in normal women (19.8% (3.8%)). No evidence of a relation between placental ratio and first antenatal visit haemoglobin concentration or mean cell volume was detected, and placental ratio was not associated with change in mean cell volume during pregnancy or with third trimester serum ferritin concentration. CONCLUSIONS: These data do not support the proposed association between poor maternal nutrition and increased placental ratio. The association between high placental ratio and adult hypertension may be confounded by genetic and environmental factors associated with maternal obesity (and possibly maternal hypertension).

Adult↗

Left ventricular diastolic function in hypertensive patients with unstable angina and single coronary artery disease.

The present study was performed to investigate left ventricular diastolic (LVD) function in hypertensive patients with unstable angina. Three groups of 17 patients each were studied. Group 1 consisted of hypertensives with unstable angina (HTU); group 2, normotensives with unstable angina (NTU); and group 3, untreated, uncomplicated hypertensives (HT). The LVD function was assessed echocardiographically by transmitral valve Doppler flow to measure the ratio between the early diastolic filling (E) and the atrial contraction phase (A). An E/A ratio of < 1 was suggestive of LVD dysfunction. Left ventricular mass (LVM), from an M-mode echocardiogram using the Penn-Cube formula, was corrected to body surface area (LVM/S) using a standard nomogram. Data are represented as median values and analyzed by Mann-Whitney test. P was significant at < .05. The HTU group had an E/A ratio of 0.8, and the NTU and HT groups had ratios of 1.17 and 1.1, respectively. There was significant diastolic dysfunction in the HTU group compared with the NTU and HT groups (P = .037 and .049, respectively). Although the LVM/S was significantly higher in the HTU group when compared with the HT group (110.6 and 96.9, respectively, P = .017), there was no significant difference between the HTU and NTU groups (123.1), P = .67. Hypertensive patients with unstable angina have significant LVD dysfunction that seems to be independent of LVM and ischemia. This may be attributable to increased stiffness of the left ventricle or structural left ventricular abnormalities.

Adult↗

The role of platelets in essential hypertension.

Recent research is helping us understand the complex interactions that occur between platelets and their environment. The several intracellular events that occur during platelet activation are being identified as ar their effects on other platelets, the endothelium and coagulation factors. Heightened platelet activation is seen early in essential hypertension and probably plays an important role in the initiation and progression of atherosclerosis and the disorders associated with it. This review identifies some of the changes in platelet structure and function in essential hypertension and their role in the pathogenesis of hypertensive vascular disease.

Blood Platelets↗

Non-transferrin bound iron and neutropenia after cytotoxic chemotherapy.

AIMS: To investigate and characterise the appearance of non-transferrin bound iron (NTBI) in the serum of patients after cytotoxic chemotherapy and to compare this with the onset and duration of neutropenia. METHOD: Non-transferrin bound iron was measured by a bleomycin assay in patients undergoing intensive chemotherapy for treatment of acute leukaemia or lymphoma. RESULTS: NTBI was detected after 26 of 27 courses of chemotherapy and lasted for a mean of 14.5 days. The presence of NTBI correlated with the serum iron binding saturation, but not with serum ferritin. Neutropenia occurred after all courses of chemotherapy and lasted for a mean of 20.0 days. NTBI and neutropenia occurred concurrently after 23 courses of chemotherapy, and had a mean joint duration of 9.5 days. CONCLUSIONS: NTBI is consistently present in the serum of patients after cytotoxic chemotherapy, often at the same time as the patient is neutropenic. This may be an additional risk factor for the development of infective episodes after chemotherapy.

Acute Disease↗