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Biomedical subjects

E M Spiers

Publications and source records attributed to E M Spiers.

25 records · Page 2Linked to original sources

Protracted systemic illness and interstitial nephritis due to minocycline.

A severe hypersensitivity-like illness with acute renal failure, lymphadenopathy and skin rash is reported following minocycline treatment in a 16 year old male. Following haemodialysis and steroid therapy his illness remitted, only to recur on withdrawal of the steroids. With further steroid treatment he recovered completely. Lymphocyte function tests, performed in an attempt to positively incriminate minocycline, were inconclusive due to a general suppression of the patient's lymphocytes to in vitro stimulation. Hypersensitivity reactions attributed to minocycline include skin rashes, lymphadenopathy and one previous case of acute interstitial nephritis.

Adolescent↗

The effect of non-steroidal anti-inflammatory drugs on phytohaemagglutinin stimulated lymphocytes: relevance to possible therapeutic immunosuppression by fenclofenac.

Representatives of seven chemical groups of non-steroidal anti-inflammatory drugs were tested for their effect on activation and replicative growth of phytohaemagglutinin stimulated normal human lymphocytes in vitro at concentrations in the high therapeutic range, and, where possible, at 10 times that concentration. Fenclofenac was noted to be suppressive. Fenclofenac and diclofenac (the only available phenylacetic acid derivatives) were studied in more detail. The two drugs were equipotent in vitro. At low concentrations they enhanced replicative growth, due to cyclo-oxygenase inhibition of cells from some subjects, but at higher concentration they suppressed replicative growth of cells from all subjects, with only a minor effect on activation at very high concentration. However, the potency for clinical effect of fenclofenac and diclofenac is very different, because fenclofenac at therapeutic blood concentrations suppressed replicative growth in vitro, whereas therapeutic concentrations of diclofenac were inactive in lymphocyte suppression. It is suggested that the phenylacetic acid derivative non-steroidal anti-inflammatory drugs may have a composite action in vivo: by inhibition of cyclo-oxygenase they reduce prostaglandin production (and so produce some symptomatic relief in the same manner as the drugs in the other chemical groups of non-steroidal anti-inflammatory agents) and by suppression of lymphocyte replication they may interfere with the pathogenesis of certain chronic rheumatic diseases.

Anti-Inflammatory Agents, Non-Steroidal↗

Mechanisms by which barbiturates suppress lymphocyte responses to phytohaemagglutinin stimulation.

Certain barbiturates (the intermediate- and short-acting drugs) reduce the growth of PHA-stimulated peripheral blood mononuclear cells, but phenobarbitone (a long-acting drug) is ineffective: replicative growth is more sensitive than activation. This action is associated with a marked reduction in the density of interleukin-2 receptors on the cell membrane and of the numbers of cells expressing them, but the growth rate cannot be restored by supplementation of the tissue culture medium with exogenous interleukin-2. The affected cells show swelling of the mitochondria and cytoplasmic fat globules: the presence of residual bodies and myelin figures indicate an increase in the rate of degradation of organelles. There was no appreciable increase in the number of necrotic cells seen on electron microscopy of cultures exposed to high concentrations of thiopentone or other potent barbiturates, but the presence of debris in the DNA cytogram at 72 h indicated some increase in the death rate of cells exposed to the growth suppressing barbiturates. It would be inadvisable to administer these short- and intermediate-acting barbiturates over long periods, particularly at high dosage, because of the potential danger of iatrogenic immunosuppression.

Adult↗

Sporotrichosis masquerading as pyoderma gangrenosum.

A 46-year-old man was diagnosed as having pyoderma gangrenosum after special stains and cultures from a skin biopsy specimen were reported as negative. Cutaneous sporotrichosis is usually diagnosed with relative ease on the basis of clinicopathologic features and prompt growth of the fungus in culture, although organisms are difficult to detect in tissue even with special stains. Identification of Sporothrix schenckii was delayed for three months in this patient because of unusual growth characteristics noted in the culture. The report of this patient's clinical course illustrates both the need to frequently reassess the diagnosis of pyoderma gangrenosum in treatment-resistant patients and the fact that S schenckii may be difficult to diagnose clinically and mycologically if the growth characteristics of the fungus are unusual.

Dermatomycoses↗