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Biomedical subjects

P Winyard

Publications and source records attributed to P Winyard.

15 recordsLinked to original sources
PubMed2001

Dysplastic and polycystic kidneys: diagnosis, associations and management.

Cystic and bright kidneys can pose a significant diagnostic dilemma when discovered as an incidental finding at the time of a routine fetal ultrasound scan. There are diverse aetiologies with equally variable implications for the prognosis in the affected fetus, and for future pregnancies. Accurate antenatal diagnosis in the absence of any positive family history is often not possible and a team approach to management (to include the fetal medicine specialist, paediatric nephrologist or urologist, geneticists and in some cases, pathologist) is essential. In this review we will attempt to describe the embryology and aetiology of these conditions and suggest an approach to management.

Adult↗
PubMed1989

Ocular toxicity of desferrioxamine--an example of copper promoted auto-oxidative damage?

Three patients with rheumatoid disease were given the 'iron chelating' drug desferrioxamine (DFX), which also has an appreciable affinity for copper. The drug was injected cautiously, in lower doses than in patients with thalassaemia, and intramuscularly to evaluate its anti-inflammatory effects. Two of the three patients developed ocular abnormalities. One patient, who also received methyldopa, developed severe but reversible visual failure associated with an abnormal electro-oculogram (EOG); another showed reversible depression of the EOG. Analysis of the cerebrospinal fluid (CSF) of this patient showed an increase in phenanthroline detectable (non-caeruloplasmin-bound) copper. Analysis of the CSF of the third patient, who did not develop any clinical or electrophysiological ocular abnormalities, was normal. Haematological assessments indicated that all three patients probably had reduced iron stores. With in-vitro systems DFX was shown to mobilise copper from albumin and to facilitate copper movement across a cell membrane model, a property that was enhanced by methyldopa. Our observations are consistent with the concept that in rheumatoid patients low iron stores may result in binding of copper by DFX and that this may be of central importance in causing the ocular toxicity of DFX.

Aged↗
PubMed1988

An automated method for the kinetic measurement of ferroxidase activity.

The oxidase activity of caeruloplasmin towards Fe II (ferroxidase) appears to be of physiological significance both in iron metabolism and as a serum anti-oxidant. We have developed an automated assay for ferroxidase using a centrifugal analyser. The method is quick and precise, and is not subject to interference by haemolysis, jaundice or lipaemia. Ferroxidase activities correlate significantly with caeruloplasmin and copper concentrations. Normal reference ranges have been measured.

Adult↗
PubMed1985

Endothelial cell cytotoxicity in inflammatory vascular diseases--the possible role of oxidised lipoproteins.

One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarteritis nodosa, Wegener's granulomatosis, and necrotising arteritis associated with rheumatoid synovitis), (2) systemic or joint restricted rheumatoid disease, and (3) large vessel/giant cell arteritis have been examined for cytotoxicity to human cultured endothelial cells and azide-resistant ferroxidase-like activity (indicative of the oxidised lipoprotein content). Stored sera from patients with necrotising arteritis showed a significantly enhanced tendency to develop oxidised lipoprotein, which correlated closely with human endothelial cell cytotoxicity. Fresh sera also contained this factor, but to a lesser extent. It is argued that the cytotoxic factor detected in previous clinical studies is in part an in-vitro artefact, although its accelerated development in certain patient groups might suggest an excess of pro-oxidants that have developed in vivo.

Arteritis↗
PubMed1985

A possible role for ferritin during inflammation.

Inflammation induces the hepatic synthesis of the iron storage protein (apo)ferritin, which is released into the circulation, and behaves as an acute phase protein. The biological significance of the extracellular rise in serum (apo)ferritin is unknown. We have observed that (apo)ferritin will stimulate superoxide production from neutrophils in the presence of cytochalasin B across a physiologically appropriate concentration range. We therefore propose that extracellular ferritin has an important role in host defence against bacteraemia by stimulating oxidative metabolism.

Animals↗
PubMed1985

Cerebral and ocular toxicity induced by desferrioxamine.

Seven patients with rheumatoid disease were given the iron-chelating drug desferrioxamine (DFX) to evaluate its possible anti-inflammatory effects. Two of these patients, who also received the anti-emetic prochlorperazine, lost consciousness for 48-72 h and then fully recovered. Electroencephalography showed abnormalities of the type associated with metabolic disturbance. One of these patients showed pyramidal features and subsequently developed an optic neuropathy and pigmentary retinopathy. Analysis of his cerebrospinal fluid showed a decrease in loosely-bound (catalytic) iron and increase in loosely-bound (catalytic) copper, total iron and products of lipid peroxidation, with values approaching normal as the symptoms resolved. Subsequent in vivo/vitro studies clearly demonstrated that the neurological effects were due to a synergistic action of desferrioxamine and prochlorperazine, probably resulting in exceptional fluxes of intra/extra cellular iron/copper disturbing noradrenergic and serotonergic systems. Two other patients who did not receive prochlorperazine, developed retinal problems which later improved, one after only 15 g of desferrioxamine. Our observations suggest a new model for metabolic encephalopathy studies and provide insight into the mechanisms of pigmentary retinopathy.

Adult↗
PubMed1984

Action of free radical generating systems upon the biological and immunological properties of caeruloplasmin.

Exposure of human caeruloplasmin, an acute phase protein with antioxidant properties, to a mixture of xanthine/hypoxanthine and xanthine oxidase as a source of reactive oxygen intermediates decreased its ferroxidase and ascorbate oxidase activities and its ability to inhibit lipid peroxidation. Immunological reactivity was also altered. Exposure to hydrogen peroxide mimicked these effects. Exposure to low-intensity u.v. irradiation depressed caeruloplasmin's ability to inhibit iron-catalysed hyaluronic acid degradation. The results may explain the mechanism of the observed inactivation of caeruloplasmin within human rheumatoid synovial fluid.

Ascorbate Oxidase↗