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Biomedical subjects

B J Hunt

Publications and source records attributed to B J Hunt.

At least 37 records · Page 2Linked to original sources
PubMed2003

Do anticoagulants improve survival in patients presenting with venous thromboembolism?

Anticoagulants have been available since around 1940 and have become the standard of treatment for venous thromboembolism (VTE) for over four decades. However, as with other treatments which became established before the evidence-based era, there is a paucity of evidence from randomized controlled trials validating their effectiveness in preventing the most feared complication of VTE, recurrent fatal pulmonary embolism (PE). Only two such trials have been performed, the results of which conflict. The bulk of data supporting their use are derived from three sources. First, studies of thromboprophylaxis, and comparisons of shorter and longer courses of anticoagulants in high-risk patients with established VTE have clearly demonstrated their effectiveness in primary and late secondary prevention. Given that heparin has an immediate onset of action, anticoagulants should therefore also be effective in early secondary prevention, the proposed mechanism of action in the acute treatment of VTE. Secondly, studies of inadequately treated patients have consistently shown higher recurrence rates than in those adequately treated. Finally, comparisons of outcomes in untreated and treated historical series, and of untreated historical series to treated series in the modern era have shown substantially lower rates of fatal PE in anticoagulated patients. Because these differences are so marked, harmonize with our current understanding of the mechanism of action of anticoagulants and are supported by other evidence, it is much more likely that they at least partly reflect the effectiveness of anticoagulants as opposed to being explicable purely in terms of accumulated biases and a changing distribution of disease severity.

Anticoagulants↗
PubMed2003

Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome.

Unresponsive autoimmune haemolytic anaemia (AIHA) may require therapy with second-line drugs. There is no consensus that any one of these agents is more effective than another. Mycophenolate mofetil (MMF) is an immunosuppressive drug proven to be effective in reducing renal allograft rejection as well as being used in autoimmune diseases including systemic lupus erythematosus (SLE). We describe its use in two patients who were treated with MMF for AIHA in the context of underlying SLE and antiphospholipid syndrome (APS). The patients showed a good response to treatment with MMF, suggesting a possible role in the treatment of AIHA.

Adult↗
PubMed2003

Cerebral haemostasis and antiphospholipid antibodies.

One of the major clinical concerns of the antiphospholipid syndrome (APS) is the propensity of antiphospholipid (aPL) antibodies to cause thrombosis in both the large and small vessels of the brain. In this article, we review the current understanding of haemostasis in cerebral circulation and discuss this in the context of antiphospholipid antibodies. The systemic-defect-local-phenotype paradox is of particular importance in this discussion. In this paradigm, a systemic defect in thrombosis and haemostasis leads to a localized pattern of thrombotic disease because the regional physiological variations in the several prothrombotic and anticoagulant factors and the defect interact so as to favour thrombosis at a particular site. One possible mechanism of initiation of thrombosis in APS is the activation of endothelial cells by aPL that could occur in the cerebral vessels and provoke thrombosis. We review the evidence from gene knockout mice, other animal models and human postmortem examination studies as to which pro- and antithrombotic mechanisms are effecting haemostasis in the cerebral circulation. We conclude that there are large deficits in the understanding of the regulation ofhaemostasis in the human brain. As a consequence there is a lack of knowledge about the effect of aPL on cerebral endothelium and thrombosis. Recent developments in gene expression profiling may have an impact on our understanding of endothelial function in the brain. More research is required.

Animals↗
PubMed2002

Antiphospholipid antibodies do not a syndrome make.

The association of antiphospholipid antibodies (aPLs) with a poor obstetric history and/or thrombotic event is typical of the antiphospholipid syndrome (APS). We report four cases of poor pregnancy outcome where a diagnostic label of APS resulted in delayed recognition of other causes of pregnancy loss. Pregnancy outcomes in these women were not improved with antithrombotic therapy alone. Successful outcomes were achieved only when other causes of recurrent miscarriage were considered and treated.

Abortion, Habitual↗
PubMed2002

Hypertension as the presenting feature of the antiphospholipid syndrome.

The antiphospholipid or Hughes syndrome is the association between antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy morbidity. Antiphospholipid syndrome (APS) commonly coexists with autoimmune diseases usually systemic lupus erythematosus (SLE), when it is known as secondary APS. When present in isolation it is known as primary APS (PAPS). Although the kidney may be affected in APS, its involvement is perhaps not as well described as that of other organs. Thrombotic microangiopathy (TMA) affecting the kidney has been reported as a manifestation in both primary and secondary APS. This report describes hypertension related to underlying renal TMA as a presenting symptom of APS.

Adult↗
PubMed2001

Effect of dissolved organic matter on the uptake of trace metals by American oysters.

To examine the effects of dissolved organic matter on metal bioavailability, uptake of trace metals (Cd, Co, Hg, Cr, Ag, Zn) by American oysters (Crassostrea virginica) was compared between treatments with different dissolved organic carbon (DOC) concentrations and contrasting low molecular weight (LMW, 1 kDa) and high molecular weight (HMW, 1 kDa-0.2 micron) DOC fractions, using radiotracer techniques and short-term exposure experiments. Uptake rate constants (mL g-1 h-1) of metals, in general, increased with increasing DOC concentrations, with an initial decrease at lower DOC concentrations. Oyster dry weight concentration factors (DCF, mL g-1), determined at the end of exposure experiments (8 h), also increased for Cd, Co, Cr, Ag, and Zn, but decreased for Hg, with increasing DOC concentrations. Changes of metal uptake rate constants and DCF values with DOC concentration suggest that metal uptake pathways by American oysters vary from predominantly uptake (by diffusion of neutral) of free ionic, inorganically complexed, and LMW organic ligand complexed metals at very low DOC concentration to direct ingestion and digestion of HMW or colloidally complexed metals at higher DOC concentrations. Measured partition coefficients (Kc) between dissolved and colloidal phases were comparable between metals, ranging from 10(5.12) to 10(5.75) mL g-1. However, DCF values and uptake rate constants differed considerably between metals, with the highest DCF values and uptake rate constants found for B-type metals, e.g., Ag, Hg, Zn, and Cd, and the lowest ones for several intermediate-type metals (e.g., Co, Cr). Metal types and thus the interaction of metals with organic ligands, such as strong complexation of B-type metals with S-containing organic ligands, may play an important role in the bioavailability and toxicity of metals to aquatic organisms. Differences in metal uptake in contrasting LMW and HMW DOC treatments suggest a generally depressed bioavailability of colloidally complexed metals at low DOC concentration (0.5 ppm) but a generally enhanced uptake at higher DOC concentrations.

Animals↗
PubMed2001

Ultrafiltration behavior of major ions (Na, Ca, Mg, F, Cl, and SO4) in natural waters.

Aquatic colloids, including macromolecules and microparticles, with sizes ranging between 1 nm to 1 micron, play important roles in the mobility and bioavailability of heavy metals and other contaminants in natural waters. Cross-flow ultrafiltration has become one of the most commonly used techniques for isolating aquatic colloids. However, the ultrafiltration behavior of chemical species remains poorly understood. We report here the permeation behavior of major ions (Na, Ca, Mg, F, Cl, and SO4) in natural waters during ultrafiltration using an Amicon 1 kDa ultrafiltration membrane (S10N1). Water samples across a salinity gradient of 0-20@1000 were collected from the Trinity River and Galveston Bay. The permeation behavior of major ions was well predicted by a permeation model, resulting in a constant permeation coefficient for each ion. The value of the model-derived permeation coefficient (Pc) was 0.99 for Na, 0.97 for Cl, and 0.95 for F, respectively, in Trinity River waters. Values of Pc close to 1 indicate that retention of Na, Cl, and F by the 1 kDa membrane during ultrafiltration was indeed minimal (< 1-5%). In contrast, significant (14-36%) retention was observed for SO4, Ca, and Mg in Trinity River waters, with a Pc value of 0.64, 0.82, and 0.86 for SO4, Ca and Mg, respectively. However, these retained major ions can further permeate through the 1 kDa membrane during diafiltration with ultrapure water. The selective retention of major ions during ultrafiltration may have important implications for the measurement of chemical and physical speciation of trace elements when using cross-flow ultrafiltration membranes to separate colloidal species from natural waters. Our results also demonstrate that the percent retention of major ions during ultrafiltration decreases with increasing salinity or ionic strength. This retention is largely attributed to electrostatic repulsion by the negatively charged cartridge membrane.

Anions↗
PubMed2001

Chronic disseminated intravascular coagulation after surgery for abdominal aortic aneurysm: clinical and haemostatic response to dalteparin.

A 77-year-old man developed chronic disseminated intravascular coagulation (DIC) after surgical repair of a large infrarenal aortic aneurysm. Self-administered subcutaneous dalteparin therapy (5000 units o.d.) led to rapid relief of symptoms and sustained improvements in his platelet count and fibrinogen level; activation of coagulation and fibrinolysis appeared to be relatively unaffected. Long-term treatment with low-molecular-weight heparin can provide good symptomatic control of chronic DIC associated with abdominal aortic aneurysm.

Aged↗
PubMed2001

The effects of aprotinin on thromboelastography with three different activators.

BACKGROUND: Thromboelastography is used for assessment of hemostasis. Adherence to thromboelastography-guided algorithms and aprotinin administration each decrease bleeding and blood product usage after cardiac surgery. Aprotinin, through inhibition of kallikrein, causes prolongation of the celite-activated clotting time and the activated partial thromboplastin ratio. The aim of this study was to assess the effects of aprotinin on the thromboelastography trace. METHODS: Three activators were used in the thromboelastography: celite (which is widely established), kaolin, and tissue factor. Assessment was performed on blood from volunteers and from patients before and after cardiac surgery. RESULTS: The tissue factor-activated thromboelastography trace was unaffected by the addition of aprotinin. When celite and kaolin were used as activators in the presence of aprotinin, the reaction time (time to clot formation) of the thromboelastography trace was prolonged (P < 0.0001) and the maximum amplitude (clot strength) was decreased (P < 0.05). With celite as an activator, the addition of aprotinin decreased (P < 0.05) the thromboelastography alpha angle (rate of clot extension). The reaction time of the celite-activated trace correlated with the activated partial thromboplastin ratio (P < 0.01). The reaction time of the tissue factor-activated trace correlated with the international normalized ratio (P < 0.01). CONCLUSION: The thromboelastography trace is altered in the presence of aprotinin when celite and kaolin are used as activators but not when tissue factor is the activator.

Aprotinin↗
PubMed2001

Venous thromboembolism after acute stroke.

BACKGROUND: Treatment for venous thromboembolism (VTE) is highly effective in preventing morbidity and mortality, yet pulmonary embolism (PE) accounts for up to 25% of early deaths after stroke. This is because the current diagnostic paradigm is reactive rather than proactive: the clinician responds to VTE when it becomes symptomatic, in the expectation that initiation of treatment will prevent progression to more serious manifestations. This approach is flawed, because sudden death from PE is frequently unheralded and nonfatal symptomatic pulmonary emboli are often unrecognized or misdiagnosed. SUMMARY OF COMMENT: Morbidity and mortality from PE could be reduced either by more effective thromboprophylaxis or earlier diagnosis and treatment of established VTE. The fact that early use of short-term, low-dose, unfractionated heparin (UFH) is not associated with sustained, clinically meaningful benefit suggests that a fundamental change in the diagnostic approach to VTE is needed, one which requires a greater appreciation that clinically apparent events are merely the tip of the thromboembolism iceberg. CONCLUSIONS: Research into a strategy of screening for subclinical VTE in these patients is needed, with a view to identifying a subgroup at risk of progression to symptomatic and life-threatening events, in whom outcome might be improved by anticoagulation.

Anticoagulants↗
PubMed2001

A genetically engineered human Kunitz protease inhibitor with increased kallikrein inhibition in an ovine model of cardiopulmonary bypass.

A recombinant human serine protease inhibitor known as Kunitz protease inhibitor (KPI) wild type has functional similarities to the bovine Kunitz inhibitor, aprotinin, and had shown a potential to reduce bleeding in an ovine model of cardiopulmonary bypass (CPB). The aim of this study was to assess KPI-185, a modification of KPI-wild type that differs from KPI-wild type in two amino acid residues and which enhances anti-kallikrein activity in a further double-blind, randomized study in an ovine model of CPB, and to compare with our previous study of KPI-wild type and aprotinin in the same ovine model. Post-operative drain losses and subjective assessment of wound 'dryness' showed no significant differences between KPI-185 and KPI-wild type, despite the significant enhancement of kallikrein inhibition using KPI-185 seen in serial kallikrein inhibition assays. These preliminary findings support the hypothesis that kallikrein inhibition is not the major mechanism by which Kunitz inhibitors such as aprotinin reduce perioperative bleeding.

Amino Acid Sequence↗
PubMed2001

von Willebrand factor-cleaving protease in childhood diarrhoea-associated haemolytic uraemic syndrome.

A deficiency of von Willebrand factor (vWF)-cleaving protease, either due to a congenital deficiency or to the presence of a protease inhibitor of vWF-cleaving protease has been associated with thrombotic thrombocytopenic purpura (TTP). We have studied vWF-cleaving protease in diarrhoea-associated haemolytic uraemic syndrome (D+ HUS), which shares clinical features with TTP. 29 children with acute D+ HUS and 13 control children were studied. vWF-cleaving protease activity was normal (range 50-150%) in 39 of 42 plasma samples. Levels of protease activity between 25 and 50% were noted in plasma from two D+ HUS patients. One D+HUS patient, who had clinical features of TTP, had a vWF-cleaving protease inhibitor producing a severe deficiency of vWF-cleaving protease. Thus a deficiency of vWF-cleaving protease appears to be atypical in D+HUS. The detection of a vWF-cleaving protease inhibitor in one patient suggests it may be associated with infection such as E. coli O157.

ADAM Proteins↗