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has been questioned. In work lately reported fromGuy’s and St. Bartholomew’s 12 an initial dose ofintravenous hydrocortisone of 4 mg/kg was adequatefor all patients, irrespective of previous treatment, andin chronic steroid-dependent asthmatics the plasmahalf-life of injected hydtocortisone was only marginallyreduced. Furthermore, patients on long-term steroidsdid not necessarily have low levels of endogenouscortisol on admission with severe acute exacerbations.In all patients studied, plasma-cortisols correlatedbest with the degree of acidsemia caused by the acuteattack.

It has been suggested that enough corticosteroidshould be given in acute severe asthma to achieve aplasma-cortisol level of 100-150 .g/d1,91 but patientshave relapsed with levels as high as 300 .g/dl.’ 3 Incontrast, some of the non-steroid-dependent patientsin the Guy’s and Barts studies did well when treatedwith a single dose of tetracosactrin; endogenousplasma-cortisol rose significantly, but to nowhere near100 g/dl. Once the mechanism of corticosteroids inasthma is clearly defined it should be possible todesign more rational dose schedules; at present itseems sensible to use a modest but adequate regimensuch as that described by the Guy’s and Barts workers.An initial dose of intravenous hydrocortisone hemi-succinate of 4 mg/kg is followed by continuous intraven-ous infusion of 3 mg/kg for the first 24-48 hours. Thisgives a total dose of little more than 1000 mg/24 h in anaverage patient and is most unlikely to produce anyadverse side-effect, though some recommend potas-sium supplements. Oral prednisolone is substitutedin high dose (e.g,; 80 mg per day) during the first 48hours of admission and tailed off as the patient im-proves. The only patients who perhaps need morethan this may be those taking phenobarbitone, whichcan almost double the metabolic clearance of cortico-steroids. 14

EMBEDDED TOENAILS

INGROWING or, more accurately, embedded 15 or" infleshed " great toenails 16 are a very common causeof pain and discomfort. Nevertheless the sufferer

commonly receives inadequate and ineffective treat-ment. Often it involves repeated visits to the doctor’ssurgery or the hospital outpatient department for

dressings, with consequent loss of time from work,school, or sport. This can be very frustrating because,although all age-groups can be affected, most patientsare in the age-range 11-30 years. In a series of 200patients, males in the second and third decadesaccounted for 56%.1’ There is clearly need for acarefully considered plan of management to dealeffectively with embedded toenails, and Murray andBedi 17 have produced an excellent survey.

If there is considerable local sepsis simple avulsion

12. Collins, J. V., Clark, T. J. H., Brown, D., Townsend, J. Q. Jl Med.1975, 44, 259.

13. Cayton, R. M., Howard, P. Thorax, 1973, 28, 567.14. Brooks, S. M., Werk, E. E., Ackerman, S. J., Sullivan, I., Trasher,

K. New Engl. J. Med. 1972, 286, 1125.15. Fowler, A. W. Br. J. Surg. 1958, 45, 382.16. Scott, P. R. Med. J. Aust. 1968, i, 47.17. Murray, W. R., Bedi, B. S. Br. J. Surg. 1975, 62, 409.

of the nail is the treatment of choice, and this cansafely be done under local anaesthesia unless there isextensive cellulitis spreading from the infected nail-folds. Avulsion allows the nail-bed to drain and the

sepsis rapidly subsides. The patient must, however,be warned that, unless great care is taken in trimmingit, the new nail will grow back in the pattern of itspredecessor. Murray and Bedi report a highrecurrence-rate after simple avulsion-64% of a

group of 145 patients. At this stage, if recrudescenceis inevitable, further avulsion should be avoided (thefailure-rate is 86% after a second avulsion). Someform of nail-bed ablation is needed. The most

effective procedure is that commonly credited to

Zadik/8 although first described by Quenu in 1877.15The nail matrix-i.e., the area corresponding to thelunula and extending proximally to the base of thedistal phalanx-is formally excised but there is no

shortening of the great toe in any way. Almost

certainly it is more effective than lesser measures suchas single or double wedge resection-that is, excisionof the medial or lateral border of the nail, or both,with the adjacent segment of nail matrix. Singlewedge resection is justified only in patients - whosesymptoms and signs have always been localised to onenail-fold and who do not want to lose the whole nail.The recurrence-rate for this procedure is 25% com-pared with 16% or lower for the Zadik procedure.For the more mature with ingrown toenails, particularlythose with vascular disease or diabetes, treatment by askilled chiropodist has much to commend it.

TROUBLESOME CANDIDA

MYCOLOGISTS have attained enviable accord on thecriteria for identifying yeast species, owing largely tothe work of Lodder, 19 to excellent reference collectionsof culture isolates, and to world-wide friendly co-operation. On the clinical front the approach to

infection with yeasts is far less purposeful; and thisis well illustrated by candida, which is evidently anincreasingly common cause of morbidity and death,especially in hospital patients. 20One reason for any irresolution in coping with

fungal infection in such patients is the difficulty ofdetermining whether the organism is a commensal or apathogen-a difficulty enhanced by the fact that thepatient is usually already debilitated from othercauses. If the fungus isolated has not been shownto obey Koch’s postulates, it is unlikely to be a patho-gen ; but repeated isolation of any fungus from thesame site in the presence of disease calls for study ofits behaviour in experimental models. It is importantto establish that the alleged source of an isolate isthe true source. Environmental contamination withCandida spp. has been reported in hospitals,21 as

has contamination of fluids for intravenous infusion. 22Pathogenic Candida spp. are unlikely to be laboratory

18. Zadik, F. R. J. Bone Jt Surg. 1950, 32B, 66.19. Lodder, J. (editor) The Yeasts: A Taxonomic Study. Amsterdam,

1970.20. Ackerman, N. B., Kronmueller, J. Surgery Gynec. Obstet. 1975, 140,

65.21. Clayton, Y. M., Noble, W. C. J. clin. Path. 1966, 19, 76.22. Deeb, E. N., Natsios, G. A. Am. J. Pharm. 1971, 28, 764.

168

contaminants and, unless diseased, the skin does notharbour them other than transiently; but they mayoccur in medicinal ointments,23 and disinfectant solu-tions or creams may act as vectors since C. albicans(the commonest pathogen in the genus) is recoverablefrom some such preparations after a lapse of eight days. 24They may contaminate containers holding drugs ofaddiction, and, in the absence of scrupulous heed tohygiene and asepsis, the impedimenta for parenteraltherapy. Removal of an infected indwelling catheterwill sometimes eradicate fungi from the urine or blood-stream without recourse to antifungal drugs, presum-ably because the inoculum is too small to initiateserious infection. In any one case, before a definitivediagnosis of mycotic disease is reached, there must beevidence of a pathological reaction to the fungus.Serological tests show promise as aids to diagnosis, butthere is need for standardisation of reagents andmethods. 25

Histological evidence of invasion, coupled withisolation of the specific agent from the site affected, isthe best evidence of an abnormal response; but it is

rarely available ante mortem. Radiological examina-tion can yield good evidence in some sites, notablythe oesophagus, and direct examination, using instru-ments for the less accessible sites, may show patho-logical changes consonant with mycotic disease of theintegument.

PSEUDOMONAS VACCINES

FEW antibiotics have therapeutic value againstPseudomonas aruginosa, and each of them has short-comings. It is therefore important to try and preventpseudomonas infection in patients with severe burns,immunodeficiency, cystic fibrosis, and other conditionsor methods of treatment that make them particularlysusceptible to invasion by these bacteria. Prophylaxiswith gentamicin or carbenicillin must be avoided,because this is most likely to lead to the emergence ofresistance. Among the alternative methods whichhave been reported to have prophylactic value, orpotential value, are active and passive immunisation.In mice invasive septicasmic infection can be preventedby injection of antiserum or of immunoglobulinfractions from antisera prepared in rabbits,26-28 andthere is evidence that patients with burns can beprotected by passive immunisation with plasma ofactively immunised volunteers. 29,30 Active immunisa-tion might have been thought to offer little or no

prospect of protection for patients with burns, butanimals very rapidly develop immunity, associated with

23. Harmon, G. A., Slutzker, B., Davis, A., Edmonds, P. Archs Derm.1962, 85, 510.

24. France, D. R. N.Z. med. J. 1968, 67, 552.25. Faux, J., Stanley, V. C., Buckley, H. R., Partridge, B. M. Br. J.

immun. Meth. 1975, 6, 235.26. Millican, R. C., Rust, J. D. J. infect. Dis. 1960, 107, 389.27. Jones, R. J., Jackson, D. M., Lowbury, E. J. L. Br. J. plast. Surg.

1966, 19, 43.28. Jones, C. E., Alexander, J. W., Fisher, M. W. Surg. Forum, 1970,

21, 238.29. Feller, I. in Research in Burns (edited by A. B. Wallace and A. W.

Wilkinson); p. 470. Edinburgh, 1966.30. Alexander, J. W., Fisher, M. W. in Gram-Negative Bacterial

Infections (edited by B. Urbaschek, R. Urbaschek, and E. Neter);p. 489. Vienna, 1975.

the appearance of antibodies in the IgM fraction,3O-33and several reports suggest that the incidence of

septicaemic infection with Ps. aeruginosa can be reducedbyactiveimmunisation with a pseudomonas vaccine. 29,30 oEven a monovalent vaccine seemed, in one series,29 tohave some prophylactic value in a burns unit, butmultivalent vaccines are needed for effective cover

against the full range of serotypes found in hospitals.Such vaccines have been developed in the UnitedStates 34,35 and in Great Britain, 36. 37 and some

evidence of their clinical value in the treatment ofseverely burned patients has been reported.30

Conflicting results have been presented on theprophylactic value of such vaccines in patients withleukaemia. 311,39 In a controlled trial of a multivalentpseudomonas vaccine in patients with acute leukaemiaand with cystic fibrosis, Pennington and others 40

now report that, while there were infections withvarious organisms in 5 of 20 unvaccinated controlpatients with leukaemia, 2 of which were caused byPs. aruginosa (1 case fatal), 14 of 22 vaccinatedleukaemics became infected, though only 1 of thesehad Ps. aerùginosa (not fatal); of 12 patients withcystic fibrosis who had the vaccine, 4 developedpseudomonas infection (with no fatality). Patientswith cystic fibrosis showed a good antibody (haem-agglutinin) response to vaccination. Leuksemicpatients showed a smaller antibody response and moretoxic effects of the vaccine, though the latter could bereduced without disturbing the former if the vaccinewas injected with an adrenal corticosteroid. Vaccinewas given to leukaemic patients when they were inbone-marrow remission and not receiving anti-

neoplastic chemotherapy.Though the proportion of infections due to Ps.

ceruginosa was smaller in the vaccinated than in theunvaccinated leukaemic patients, the numbers-in thetrial were much too small for an assessment of theclinical usefulness of active immunisation. The

antibody production, however, was good, and providedindirect evidence of a probable enhancement, byopsonic action, of the patients’ defence against pseu-domonas invasion. In the patients with cystic fibrosisthere was a much greater production of antibody inresponse to vaccination; none of these patients diedwith pseudomonas septicaemia, and it may be assumedthat they were well protected against systemic invasion.The failure of vaccination to eradicate Ps. xruginosafrom the sputum and to reduce the clinical severityof the disease in these patients is not surprising, forno antibody responses to vaccination were found in therespiratory-tract secretions except in one of the

patients.

31. Markley, K., Smallman, E. J. Bact. 1968, 96, 867.32. Jones, R. J., Lowbury, E. J. L. Br. J. exp. Path. 1972, 53, 659.33. Jones, R. J., Hall, M., Ricketts, C. R. Immunology, 1972, 23, 889.34. Alexander, J. W., Fisher, M. W., Macmillan, B. G., Altemeier, W. A.

Archs Surg. 1969, 99, 249.35. Hannessian, S., Regan, W., Watson, D., Haskell, T. H. Nature

New Biol. 1971, 229, 209.36. Jones, R. J. J. Hyg., Camb. 1972, 70, 343.37. Miler, L. Unpublished.38. Young, L. S., Meyer, R. D., Armstrong, D. Ann. intern. Med.

1973, 79, 518.39. Haghbin, M., Armstrong, D., Murphy, M. L. Cancer, 1973, 32,

761.40. Pennington, J. E., Reynolds, H. Y., Wood, R. E., Robinson, R. A.,

Levine, A. S. Am. J. Med. 1975, 58, 629.