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Biomedical subjects

D R Blake

Publications and source records attributed to D R Blake.

At least 235 records · Page 13Linked to original sources
PubMed1987

Raised cerebrospinal-fluid copper concentration in Parkinson's disease.

The cerebrospinal-fluid copper concentration, measured by electrothermal atomisation/atomic absorption spectrophotometry, was significantly higher in 24 patients with untreated, idiopathic Parkinson's disease than in a control population of 34 patients (p less than 0.001). The difference in the in-vitro capacity of copper to damage DNA, measured by the phenanthroline assay was even greater. The high phenanthroline-copper concentration correlated with disease severity (p = 0.02) and with the rate of progression of disease (p less than 0.05). A possible role is suggested for copper-catalysed oxidative mechanisms in the pathogenesis of Parkinson's disease.

Adult↗
PubMed1987

Mechanism of exacerbation of rheumatoid synovitis by total-dose iron-dextran infusion: in-vivo demonstration of iron-promoted oxidant stress.

The mechanism by which a synovial flare occurred in a patient with rheumatoid arthritis after intravenous infusion of iron-dextran was investigated. After the infusion, serum and synovial-fluid iron-binding capacity became saturated, giving rise to low-molecular-mass iron chelates with the capacity to cause oxidative damage ("bleomycin-iron"). At the same time lipid peroxidation and the concentration of oxidised ascorbic acid (dehydroascorbate) increased in both serum and synovial fluid, and red-cell glutathione fell. These changes corresponded closely to an exacerbation of rheumatoid synovitis. Hepatic function was transiently disturbed 7 days after the infusion, reflecting hepatic oxidant stress within the iron-loaded liver. Such changes provide clear evidence that iron-catalysed oxidative reactions influence the inflammatory process in human beings.

Arthritis, Rheumatoid↗
PubMed1987

Xanthine oxidoreductase is present in human synovium.

It is postulated that the mobile inflamed joint may be subject to cyclical ischaemic reperfusion injury. Xanthine oxidoreductase is an enzyme thought to contribute to oxidative reperfusion injury, and the detection of this activity in human synovium is described. Three normal and five rheumatoid tissues were assayed with a carbon-14 radioassay detecting the conversion of [14C]xanthine to [14C]uric acid. Rheumatoid synovia contained 0.67-305 microU/g tissue (n = 5), while normal synovia contained 1.2-5.0 microU/g tissue (n = 3).

Allopurinol↗
PubMed1987

Effect of nutritional iron deficiency on acute and chronic inflammation.

Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.

Acute-Phase Proteins↗
PubMed1987

Effect of free radical altered IgG on allergic inflammation.

The rheumatoid synovium is capable of producing large amounts of IgG which may become modified by the actions of free radicals. A rat model of synovitis was established and challenged with both normal and free radical altered IgG. IgG was prepared from homologous pooled serum by high performance liquid chromatography, and free radical damage was induced by 15 minutes ultraviolet (UV) irradiation. The results showed a worsening in gross assessments of inflammation, increases in biochemical indices of lipid peroxidation, and also a rise in the proportion of IgG which, on reisolation, showed the characteristic fluorescence associated with free radical damage. This demonstrated how the presence of free radical altered IgG might convert an inflammatory insult to a more persistent stimulus, and the capacity of an environment subjected to continuing antigenic stimulation to induce further free radical damage to IgG.

Animals↗
PubMed1987

Renal impairment associated with non-steroidal anti-inflammatory drugs.

We have compared the renal function on admission and discharge of 22 patients routinely admitted to our rheumatology ward. None had previously diagnosed renal failure. Of 11 patients in whom we stopped long term non-steroidal anti-inflammatory drug (NSAID) therapy, all showed a rise in creatinine clearance (Ccr) after three to 28 days. In contrast, a control group comprising 11 similar patients who continued to receive NSAIDs showed no significant change. Recent work has suggested that it is possible to identify patients at risk of developing nephrotoxic side effects with NSAIDs. Based on these criteria (but excluding age alone as a risk), six patients from the first group and 10 from the second group would have been without risk. We infer from this that asymptomatic, reversible impairment of renal function is common, and that the potential clinical benefit from the use of NSAIDs should be balanced against this predictable toxicity.

Adult↗
PubMed1987

Effect of iron chelation on inflammatory joint disease.

Mild iron deficiency induced by treatment with the iron chelator desferrioxamine reduced the incidence and severity of joint inflammation associated with adjuvant disease in rats but did not alter the local primary inflammatory response or the systemic sequelae. Both rats treated with desferrioxamine and control rats showed increased levels of alpha 1 acid glycoprotein, characteristic pathological changes in the liver and inguinal lymph nodes, and the primary inflammatory response at the site of injection. Histology, microfocal radiography, and gross assessment of the joints, however, showed a suppression or reduction in soft tissue swelling and bone erosion in the rats treated with desferrioxamine. This is a novel observation suggesting an apparently selective influence of iron on joint mediated inflammation.

Animals↗
PubMed1987

Macrophage ferritin and iron deposition in the rat air pouch model of inflammatory synovitis.

Using a rat air pouch model of red cell promoted allergic inflammation, we have investigated the relation between ferritin synthesis and iron deposition in pouch wall lining cells. These cells have structural and immunohistochemical similarities to human synovial intimal cells and studies of them are pertinent to the clinical situation. In control air pouch wall tissue after single or double antigenic challenge the (apo)ferritin containing macrophages are most numerous seven days after antigenic challenge when there is active connective tissue proliferation and a generalised mononuclear cell response in the pouch wall, suggesting that (apo)ferritin is produced in macrophages as part of the tissue inflammatory response. In contrast with control tissue, where there is a steady decrease in positive cells over the ensuing weeks, injection of blood into both single and double challenge air pouches produces a significant (p less than 0.001) and continuing rise in the numbers of ferritin containing macrophages after day 7. Also, after 14 days Perls' positive ferric iron is detectable in increasing numbers of ferritin containing macrophages, a trend which is more marked in double challenge, blood injected air pouches. The histological data clearly show that there is a close relation between the presence of Perls' iron and proliferation of vascular and connective tissue elements in the pouch wall. We propose that this proinflammatory role of iron is the result of its ability to promote oxidative damage in tissues, and discuss ways in which this may take place.

Animals↗
PubMed1987

Serum salicylate levels in a breast fed infant.

All drugs should be given with caution to pregnant or breast feeding women. Recent concern about the role of salicylates in the aetiology of Reye's syndrome has prompted the DHSS to restrict the use of aspirin in children. The case of a 9 week old breast fed infant whose serum contained 0.47 mmol/l of salicylate is reported. Her mother was taking aspirin 2.4 g/day, and it is concluded that salicylates must not be taken by breast feeding mothers.

Adult↗
PubMed1986

Iron and akathisia.

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Akathisia, Drug-Induced↗