1. McEwen, L.M., Ganderton, M.A., Wilson, C.W.M., Black, J.H.D., Hyaluronidase in the treatment of allergy, Brit. Med. J. (1967) 2: 507-508.
2. McEwen L.M. Effects of sugars and diols on enzyme potentiated hyposensitisation. J. Physiol. 1972. 230: 65-66.
3. McEwen L.M., Starr M.S. Enzyme Potentiated Hyposensitisation I, Int. Arch Allergy. 1972. 42: 152-158. glucuronidase and hyaluronidase was used to potentiate the hyposensitising effect of injected antigen into laboratory animals. Guinea pigs were injected with egg albumin, rats and mice with horse serum and all showed a hyposensitising effect following glucuronidase and hyaluronidase pre-treatment.
4. McEwen L.M. Enzyme Potentiated Hyposensitisation II, Annals of Allergy 1973. 31: 79-83. In mice sensitised to horse serum, glucuronidase prevents the increased sensitivity which results from a second dose of antigen. glucuronidase loses this activity with age or in the presence of gelatin. In both cases glucose will restore the immunological blocking activity of the enzyme. These results give a reason for the previous variability expressed using different samples of enzyme in earlier experiments. As well as glucose, glucosamine and N-acetyl amino sugars have a similar effect.
5. McEwen L.M., Mary Nicholson, Kitchen I, Sheila White: Enzyme Potentiated Hyposensitisation III: Control by sugars and diols of the immunological effect of glucuronidase in mice and patients with hay fever. Annals of Allergy. 1973. 31: 543-550. The ability of glucuronidase and a small dose of antigen to modify the anaphylactic reaction of previously sensitised mice has been further investigated. A 1-3 diol structure appears to be most effective in controlling the hyposensitising effect of the enzyme, although some concentrations have the opposite effect of hypersensitisation. The dose response curve is W shaped. A clinical trial on hay fever patients confirms that the results for the diol in mice are clinically relevant.
6. McEwen L.M., Mary Nicholson, Kitchen I., O'Gorman J., Sheila White: Enzyme Potentiated Desensitisation IV. Effects of protamine on the immunological behavior of glucuronidase in mice and patients with hay fever. Annals of Allergy 1975. 34: 290-295. Using mice pinnal anaphylaxis, the addition of protamine sulphate to the glucuronidase/diol mixture displaced the dose response curve, with less diol being required to achieve the same immunological effect. Hay fever patients also produced similar results. It is suggested that the protamine helps to stabilise the enzyme mixture, minimising the effect of contaminant proteins.
7. J.W. Hadden, R.G. Coffey, E.M. Hadden, E. Lopez-Corrales and G.H. Sunshine: Effects of Levamisole and Imidazole on Lymphocyte Proliferation and Cyclic Nucleotide Levels
These (above) early reports were published during the development of EPD.
8. McEwen L.M: Enzyme Potentiated Hyposensitisation V: Five case reports of patients with acute food allergy. Annals of Allergy 1975. 35: 98-103. Case reports of five patients successfully hyposensitised to foods including one lady highly sensitive to eggs. Other cases were sensitive to eggs, milk, fruit and nuts.
9. McEwen L.M. Hyposensitisation. In:Brostoff J and Challacombe SJ, Eds Food allergy and intolerance. London; Bailliere Tindall, 1987. 985-994.
10. Fell P., Brostoff J. A single dose desensitisation for summer hayfever. Results of a double- blind study – 1988. Eur. I. Clin. Pharmacol. (1990) 38; 77-79.
11. Egger J., Stolla A, McEwen L.M. Controlled trial of hyposensitisation in children with food induced hyperkinetic syndrome. Lancet (1992) 339; 1150-1153.
12. Longo G., Poli F. Bertoli G. Efficacia clinica di un nuovo trattamento iposensibilizzante, EPD (Enzyme potentiated desensitisation) nella terapia della pollinosi. Riforma Med. (1992) 107; 171-176.
13. Astarita C., Scala G., Sproviero S., Franzese A. A double blind placebo controlled trial of enzyme potentiated desensitisation in the treatment of pollenosis. J. Invest. Allergol. Clin Immunol., (1996); 6(4):248-255.
14. AngeliniG., Curatoli G., D’Argento V., Vena G.A. Pollinosi: Una nuova metodica di immunoterapia. Medit. J. Surg Med (1993), 253-256. These Italian studies looked at EPD in the treatment of asthma and hay fever.
15. Cantani A., Monteleone M.A., Ragno V., Lucenti P., Buscino L. Enzyme potentiated desensitisation in children with asthma and mite allergy; A double blind study. J. Invest. Allergol. Clin. Immunol., (1996); 6(4); 120, 270-276.
16. Ippoliti F., Ragno V., Del Nero A., McEwen L., McEwen H.C., Businco L. Effect of preseasonal enzyme potentiated desensitisation (EPD) on plasma IL-6 and IL-10 of grass pollen-sensitive asthmatic children. Allergie et Immunologie. (1997); 29(5); 120, 123-125.
17. Egger J., Stolla A., McEwen L.M. Controlled trial of hyposensitisation in children with food-induced migraine. Cephalagia, (1993); 13, (suppl.13); 216.
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