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Biomedical subjects

B J Hunt

Publications and source records attributed to B J Hunt.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

Risk of lymphoid neoplasia after cardiothoracic transplantation. a cohort study of the relation to Epstein-Barr virus.

BACKGROUND: Organ transplantation is associated with a greatly increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD), which is often fatal. There has been little epidemiological analysis, however, of the risk factors for LPD in transplant patients and none on whether the risks of non-EBV-associated lymphoid neoplasms are also increased. METHODS: The risk of lymphoid neoplasia was assessed in a cohort of 1563 patients who underwent cardiothoracic transplantation at Harefield Hospital, UK from 1980 to 1994 and were followed until December 1995. EBV antibody was assessed in the patients before transplantation, and lymphoid neoplasms were assessed for EBV RNA and latent EBV gene expression. RESULTS: Thirty cases of LPD occurred during follow-up. One lymphoma of unknown EBV status occurred. There were also six cases of EBV-negative non-Hodgkin's lymphoma (EBV-negative NHL), a highly significant excess over expectations from the general population rates of NHL (standardized incidence ratio 10.2 [95% confidence interval, 4.6-22.8]). The risk of LPD was significantly 10-fold raised in individuals who were EBV seronegative before transplantation; independently of this, it decreased steeply with age at transplantation and was greatest in the first year after transplantation. The risk was significantly raised in young seronegative recipients if the donor was older than the recipient. EBV-negative NHL occurred entirely in men 45 years old and older who were EBV seropositive before transplantation, and risk was not related to duration since transplantation. CONCLUSIONS: The risk factors found for LPD accord with EBV etiology and with greater hazard from primary infection than from reactivation. A second non-Hodgkin's lymphoid neoplasm, not related to EBV, seems also to be a consequence of transplantation and immunosuppression but is unlikely to be due to first infection by a ubiquitous agent. Its etiology and prevention need investigation separately from LPD.

Adolescent↗

Antiphospholipid antibodies and the endothelium.

This article reviews current understanding of the relationship between antiphospholipid antibodies and the endothelium. In vitro antiphospholipid antibodies produce endothelial cell activation. Clinical data in this area are scanty and worthy of future research, which could lead to new therapies in the management of antiphospholipid syndrome.

Antibodies, Antiphospholipid↗

Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting.

BACKGROUND: Aspirin therapy is widely used in the treatment of cardiac disease. It has been recognized as a causative factor for increased bleeding and blood loss after open heart operations. METHODS: To determine whether high-dose aprotinin maintained its efficacy in reducing blood loss in the presence of aspirin pretreatment in patients undergoing aortocoronary bypass, we performed a double blind study on 60 adult patients. Half received high-dose aprotinin (Trasylol) and half placebo. RESULTS: Total hemoglobin loss, the primary efficacy variable was reduced from 36.1 +/- 31.4 g (mean +/- SD) to 14.1 +/- 16.0 g (p = 0.002). Blood loss was reduced intraoperatively and total loss was reduced from 837.3 mL +/- 404.9 mL to 368.7 mL +/- 164.3 mL (p < 0.001). The number of patients who did not receive any donor blood products was significantly higher in the aprotinin-treated patients (56.7% versus 23.3%, p = 0.008). Activation of the clotting cascade was significantly less in the treated patients toward the end of cardiopulmonary bypass both by measurement of thrombin-antithrombin III complex (p < 0.0001) and prothrombin fragment 1 + 2 (p < 0.0001). D-Dimer generation was significantly less from the onset of bypass and after reversal of heparin in the aprotinin-treated patients (p < 0.0001). CONCLUSIONS: High-dose aprotinin was highly effective in reducing bleeding in this high-risk group of patients. Biochemical analyses suggest the mechanism by which aspirin increases blood loss after cardiopulmonary bypass is different from the blood-preserving effects of aprotinin, which is acting as an antifibrinolytic agent.

Adult↗

Widespread cutaneous necrosis occurring in association with the antiphospholipid syndrome: a report of two cases.

The antiphospholipid syndrome is an acquired prothrombotic state where thrombosis and/or pregnancy loss is related to the presence of antiphospholipid antibodies. Cutaneous necrosis secondary to intravascular thrombosis of small dermal vessels is a recognized but rare association with antiphospholipid syndrome. We report two patients with high circulating levels of anticardiolipin antibodies who developed widespread cutaneous necrosis as the first clinical manifestation of the antiphospholipid syndrome. The exact mechanism by which antiphospholipid antibodies mediate thrombosis is uncertain; however, proposed mechanisms of activity include endothelial cell activation, altered endothelial production of prostacyclin, activation of platelets, and modulation of the protein C and S pathways.

Aged↗

Non-steroidal anti-inflammatory drugs as a possible cause for reversible infertility.

OBJECTIVE: To highlight the possible association between infertility and treatment with long-term non-steroidal anti-inflammatory drug (NSAIDs). NSAIDs act mainly through the inhibition of cyclooxygenase, the enzyme that catalyses the synthesis of prostaglandins, which are essential mediators of ovulation, implantation and placentation of the conceptus. METHODS: Case reports of four women suffering from severe arthritis, on long-term NSAIDs and undergoing extensive investigation and treatment for infertility. RESULTS: During the last 2 yr, four out of five women with severe arthritis and difficulty conceiving were counselled to stop NSAIDs, and they successfully conceived shortly after the withdrawal of NSAIDs. CONCLUSION: NSAIDs, used largely for the treatment of rheumatological conditions, may be responsible for some cases of infertility.

Adult↗

The endothelium in atherogenesis.

The focus of this article is an overview of the endothelial changes that initiate and perpetuate the process of atherogenesis. The endothelium can undergo a series of changes which allow it to participate in the inflammatory response; this is known as endothelial cell activation (ECA). The five core changes of ECA are loss of vascular integrity; expression of leucocyte adhesion molecules; change in phenotype from antithrombotic to prothrombotic; cytokine production, and upregulation of HLA molecules. The diverse effects of ECA share a common intracellular control mechanism through the activation of the transcription factors including Nuclear Factor kappaB. ECA is an initiating step in atherogenesis. Modified low density lipoproteins are probably the major cause of endothelial cell activation in atherogenesis, and become especially so after oxidation, glycation (in diabetes) or incorporation in immune complexes. In antiphospholipid syndrome (APS), antiendothelial cell antibodies have been detected in up to 67% of patients. In vitro studies suggest that aPL causes ECA and thus lead to speculation that aPL by causing ECA may initiate atherogenesis. Further clinical and in vitro studies are required to address these issues.

Antiphospholipid Syndrome↗

Systemic endothelial cell markers in primary antiphospholipid syndrome.

The pathogenic mechanism underlying the prothrombotic tendency of Hughes' or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.

Adult↗

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial.

BACKGROUND: Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. METHODS: 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. FINDINGS: Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). INTERPRETATION: Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Adult↗

Markers of endothelial cell activation and injury in childhood haemolytic uraemic syndrome.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin-producing Escherichia coli. Histology shows endothelial swelling with localised thrombus. Activation of coagulation and fibrinolysis also occurs. These facts, combined with the knowledge that recovery usually follows within weeks, led us to hypothesise that verotoxin causes localised endothelial cell activation but not injury. Markers of endothelial cell activation and injury were measured serially in 30 children with acute D+ HUS, healthy children, and children receiving chronic dialysis. Interpretation of markers was complicated by the renal dysfunction characteristic of D+ HUS. Nevertheless there was no evidence for endothelial cell injury, as soluble tissue factor levels were not increased and soluble thrombomodulin levels were lower than dialysed controls (P<0.001). In the acute phase, soluble vascular cell adhesion molecule levels were raised above normal (P<0.001), but were lower than dialysed controls (P<0.001), and soluble E-selectin levels were not significantly increased compared with normal controls (P=0.2). Hence, there was no evidence for endothelial cell damage or endothelial cell activation by the time children reached hospital; but this study did not exclude the possibility that endothelial cell activation occurred prior to hospital admission.

Adolescent↗