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Biomedical subjects

Beverley J Hunt

Publications and source records attributed to Beverley J Hunt.

31 records · Page 2Linked to original sources
PubMed2003

Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis.

Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P <or= 0.006). The ischaemic leukoaraiosis group had a different endothelial marker profile, with lower levels of TFPI (P = 0.01) and a higher TF/TFPI ratio (P = 0.01) compared with the isolated lacunar infarction group. TM levels were associated with the number of lacunes (P = 0.008) and the leukoaraiosis score (P = 0.03), but TF levels and the TF/TFPI ratio were associated only with the extent of leukoaraiosis (P <or= 0.02). These results suggest that there is evidence of chronic endothelial dysfunction in cerebral SVD, and endothelial prothrombotic changes may be important in mediating the ischaemic leukoaraiosis phenotype. Therapies which help to stabilize the endothelium may have a role in this group of patients.

Aged↗
PubMed2003

The relationship between acute ischaemic stroke and plasma D-dimer levels in patients developing neither venous thromboembolism nor major intercurrent illness.

The true relationship between plasma D-dimers and acute ischaemic stroke (AIS) is uncertain as previous studies investigating this have not screened for subclinical deep vein thrombosis. We addressed this as part of a study in which we screened AIS patients for venous thromboembolism (VTE). We also assessed the performance characteristics of two D-dimer assays as exclusionary tests for VTE in these patients. One hundred and two unselected AIS patients were screened for VTE using magnetic resonance direct thrombus imaging. D-dimers were analysed on days 2, 9, 14 and 21 using the VIDAS immunofluorescent assay (cut-off >or= 500 ng/ml) and the IL test D-dimer immunoturbidimetric assay (cut-off >or= 255 ng/ml). The relationship between D-dimers and AIS was examined in 52 patients neither developing VTE nor intercurrent illness. D-dimers were elevated throughout the study. Median values at the four time points were 652, 692, 737 and 686 ng/ml (VIDAS assay) and 260.5, 268.5, 273 and 283 ng/ml (IL assay). D-dimers were higher in patients aged older than 70 years, with severe stroke or with total anterior circulation infarcts: only age older than 70 years was significantly associated with D-dimer values greater than the median on univariate and multivariable analysis. Both assays were 100% sensitive for VTE. Specificities were 30% (VIDAS assay) and 34% (IL assay). Specificity was adversely affected by age older than 70 and severe versus non-severe stroke. D-dimers are elevated in the first 3 weeks post-AIS after eliminating the confounding effect of subclinical deep vein thrombosis. The VIDAS and IL assays remained sensitive tests for VTE but the specificity was low, limiting their exclusionary efficiency in these patients.

Acute Disease↗
PubMed2003

Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event.

The comparatively high rate of complications, both to the mother and foetus, of warfarin and unfractionated heparin have led to an increased use of low molecular weight heparins (LMWH) in pregnant women at risk of thrombosis. However, despite reliable pharmacokinetics of LMWH, current practice is that anti-activated factor X levels are monitored in this group of patients. We report the use of unmonitored dalteparin in 27 pregnancies of 25 women who had previous thrombotic events. All women had normal renal function and weighed less than 85 kg prior to conceiving. The regimen consisted of 5000 IU dalteparin once daily started at the time of a positive pregnancy test, and increased to twice daily at 16-20 weeks gestation. In this cohort of patients there was a low complication rate. None of the women developed recurrent venous thromboses during these pregnancies but two women with known cerebral antiphospholipid syndrome developed recurrent cerebral ischaemia, which responded to an increase in dose. In our small group of patients, we have found that the use of intermediate-dose LMWH in pregnant women does not need to be monitored, and that it is safe and probably effective in preventing recurrent venous but not arterial thromboembolic events in high-risk pregnancies.

Adult↗
PubMed2003

Magnetic resonance direct thrombus imaging: a novel technique for imaging venous thromboemboli.

Invasive testing is now seldom required in patients with suspected venous thromboembolism (VTE). However, a corollary of noninvasive imaging is increased complexity as results are often yielded as probabilities rather than definitive answers and additional testing is frequently required following initial imaging. This creates a milieu in which misunderstandings and protocol violations are common, potentially leading to diagnostic errors. A highly accurate noninvasive imaging technique which allows immediate treatment decisions to be made is needed. Magnetic resonance direct thrombus imaging (MRDTI) is a novel technique which detects methaemoglobin in clot, allowing visualisation of thrombus without using intravenous contrast. It has two major advantages over conventional modalities which identify it as having the potential to fill this role. Firstly, direct visualisation of thrombus overcomes many of the pitfalls of conventional techniques, which have either identified thrombus as a filling defect or in terms of surrogates. Secondly, simultaneous imaging of the legs and chest allows a comprehensive assessment of thrombus load, minimising the importance of overlooked subsegmental pulmonary embolism (PE) and potentially facilitating more titrated treatment. Early data suggest MRDTI is highly accurate for the detection of both deep vein thrombosis (DVT) and PE, and ongoing out-come studies are evaluating the safety of withholding treatment in suspected DVT and PE on the basis of negative MRDTI alone. If favorable, a multi-centre outcome study evaluating cost-effectiveness as well as safety would be justified. Subject to further evaluation, this technique has the potential greatly to simplify and standardise the investigation of suspected VTE.

Algorithms↗
PubMed2002

Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5.

BACKGROUND: Prolonged anticoagulation is the treatment of choice for patients with thrombosis and the antiphospholipid syndrome. However, there is still debate about the optimum intensity of anticoagulation. METHODS: The study included 66 patients with antiphospholipid syndrome (Sapporo criteria) and previous thrombosis. All were receiving oral anticoagulation to a target international normalized ratio of 3.5. Every patient was individually interviewed to recall major bleeding and thrombotic episodes during the previous 12 months. RESULTS: Patients were mainly women and white. The rate of major bleeding was 6 cases per 100 patient-years (95% confidence interval [CI] 1.6-15.0). The rate of intracranial bleed was 1.5 per 100 patient-years (95% CI, 0.04-8.4). None of the bleeding episodes was fatal. The rate of thrombotic recurrences was 9.1 cases per 100 patient-years (95% CI, 3.3-19.6). Most recurrences took place in the same vascular bed as the original thrombosis. Age, time receiving anticoagulant therapy, primary vs secondary antiphospholipid syndrome, positivity for anticardiolipin antibodies, positivity for lupus anticoagulant, previous arterial thrombosis, previous stroke, previous venous thrombosis, and previous thrombocytopenia were not predictive of bleeding events. However, the risk of thrombotic recurrences was independently higher in patients who were receiving anticoagulation for longer periods. CONCLUSIONS: The risk of intracranial and fatal bleeding in patients with definite antiphospholipid syndrome and previous thrombosis treated with oral anticoagulation to a target international normalized ratio of 3.5 is similar than in groups of patients treated to lower target ratios. The risk of thrombotic recurrences, even during anticoagulation, was high. Most recurrences took place in the same territory as original thromboses.

Adolescent↗
PubMed2002

Plasma D-dimers in the diagnosis of venous thromboembolism.

Clinical suspicion for venous thromboembolism (VTE) mandates objective testing to confirm or exclude the diagnosis. However, current imaging modalities are imperfect because of a small but important risk of complications with invasive techniques or limited sensitivity with noninvasive ones. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. Plasma D-dimers (D-ds), specific cross-linked fibrin derivatives, partially fulfill these criteria in that they are sensitive markers for thrombosis but lack specificity. They therefore cannot be used to make a positive diagnosis of VTE; however, they generally have high negative predictive value and are useful as an exclusionary test, a potentially important role given that VTE is eventually ruled out in most patients investigated. Clinical management studies are clarifying the role of D-ds in the diagnostic paradigm of VTE: negative ultrasound and D-d findings obviate the need for serial imaging in suspected deep vein thrombosis, and anticoagulant therapy can be safely withheld in patients with non-high clinical suspicion for pulmonary embolism and non-high probability ventilation perfusion scan if D-d test results are negative. More recently, the combination of a negative SimpliRED (AGEN Biomedical Ltd, Brisbane, Australia) D-d result and low clinical suspicion derived using a formal scoring system has been shown to exclude deep vein thrombosis and pulmonary embolism and to obviate the need for imaging. Several different D-d assays are now available, and clinicians should be aware of the performance characteristics of the test used before incorporation into diagnostic algorithms as these will differ between assays, and the results of clinical management studies cannot necessarily be safely extrapolated to assays other than those specifically evaluated. If alternative assays are to be substituted, these should consistently have been shown to possess equivalent or greater sensitivity.

Biomarkers↗
PubMed2002

A longitudinal study of biochemical variables in women at risk of preeclampsia.

OBJECTIVE: The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preeclampsia in the blood of pregnant women in whom preeclampsia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preeclampsia and with women who were at low risk for the development of preeclampsia. STUDY DESIGN: This was a prospective case control study. The subjects were women at risk of preeclampsia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preeclampsia developed later, in 17 women without preeclampsia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preeclampsia. RESULTS: Ascorbic acid was reduced early in preeclampsia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preeclampsia. CONCLUSION: Gestational profiles of several markers were abnormal in the group with preeclampsia, and some of the markers that may prove useful in the selective prediction of preeclampsia were identified.

Algorithms↗
PubMed2002

Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function.

OBJECTIVE: We have previously reported a reduced incidence of preeclampsia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preeclampsia. STUDY DESIGN: Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously. RESULTS: Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased; and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk. CONCLUSION: Antioxidant supplementation in women who were at risk of preeclampsia was associated with improvement in biochemical indices of the disease.

Adult↗
PubMed2002

Pulmonary embolism and pneumonia may be confounded after acute stroke and may co-exist.

Pulmonary embolism and pneumonia are prevalent complications after acute stroke that overlap significantly in their timing, risk factors and clinical features. Consequently, confounding and co-existence of these diagnoses can occur and is probably commoner than is generally appreciated. Correct identification of pulmonary embolism in these patients is important as the mortality of this condition following stroke is higher than in unselected patients. Clinicians should have a low threshold for suspicion of, and objective testing for, pulmonary embolism in stroke patients with acute cardiorespiratory symptoms, even if an alternative diagnosis is evident.

Humans↗