360 trol group scores were estimated against variance between subjects, and change over time and interaction between groups over time estimated against residual variance. For significant F-ratios a Newman-Keuls test’ was performed to determine the significance of differences between each pair of means.

Hypothesis OCCLUSION, CARBON DIOXIDE, AND FUNGAL SKIN INFECTIONS

RESULTS

supraliminal and subliminal groups showed significantly greater improvement in phobic fears, avoidance, and overall improvement than did the control group. There was little difference between the subliminal and supraliminal groups and for only one rating, depression, was there a significantly greater improvement in the subliminal group (table II and figure). DISCUSSION

The results suggest that repeated exposure to agorastimuli in the form of cine-film under both subliminal and supraliminal viewing conditions is useful in reducing phobic symptoms. The changes leading to improvement could be related to habituation8 or desensitisation, although the latter term does not seem appropriate since patients were given no relaxation training and were not asked to think about phobic situtations during exposure of the film; flooding is also an inappropriate term since the phobic stimuli were intermittent rather than continuous. The frequent assessments might have led to some non-specific improvement, but such effects would apply also to the control group. The absence of a placebo response in the control group (who deteriorated slightly) emphasises the chronicity of the patients treated. The greater improvement in depression scores in the subliminal group suggests that subliminal exposure, at least initially, may be more suitable than supraliminal exposure for those patients who find phobic confrontation particularly distressing. The patients were at a loss to explain their improvement and several concluded that the "treatment" was a complex way of telling them that they had to solve their problems through their own efforts. When they did improve, their self-esteem was greatly enhanced as they believed little or no external help had been given. Previous work with subliminal stimuli has been largely concerned with eliciting dynamic psychopathology.9,lo Our results justify further inquiry into subliminal therapy for phobic and other affective disorders.

phobic

We thank Judith Leathart and Ian Churchill from the department of teaching media, University of Southampton, for making the films used in the study. Requests for reprints should be addressed to P.T., South Academic Block, Southampton General Hospital, Tremona Road, Southampton S09 4XY.

REFERENCES

Wolpe, J. J. nerv. ment. Dis. 1961, 132, 189. Watson, J. P., Gaind, R., Marks, I. M. Br. med. J. 1971, i, 13. 3. Boulougouris, J. C., Marks, I. M. Br. med. J. 1969, ii, 721. 4. Crowe, M. J., Marks, I. M., Agras, W. S., Leitenberg, H. Behav. Res.

ROBERT D. KING

ALFRED M. ALLEN

Both the

1. 2.

Ther.

1972, 10, 219. 5. Gelder, M. G., Marks, I. M., Wolff, H. H. Br. J. Psychiat. 1967, 113, 53. 6. Tyrer, P., Lewis, P., Lee, I. J. nerv. ment. Dis. 1978 166, 88. 7. Winer, B. J. Statistical Principles in Experimental Design. New York, 1970. 8. Lader, M. H., Wing, L. Physiological Measures, Sedative Drugs, and Morbid Anxiety; p. 13. London, 1966. 9. Shevrin, H. Psychol. Issues, 1973, 8, 56. 10. Silverman, L. H. Int. Rev. Psycho-Analysis, 1975, 2, 43.

Department of Dermatology Research, Letterman Army Research, San Francisco, California 94129, U.S.A.

Institute of

Occlusion of the skin renders it susceptible to acute fungal skin infections (dermatophytosis and candidiasis). Occlusion also raises carbon-dioxide (CO2) tensions at the skin’s surface. Comparable CO2 tensions have a pronounced effect on the morphology and metabolism of dermatophytes in vitro. It is postulated that dermatophyte conidia and hyphæ produce infective units under conditions of raised CO2 tensions, and that occlusion of the skin produces the concentrations of CO2 required for the conversion. Fungal skin infections might be prevented or controlled by interference with the action of CO2 or by prevention of its accumulation under wet, occlusive clothing.

Summary

INTRODUCTION

OCCLUSION of the skin has

a

profound various

effect in prodisof skin by an

ducing, aggravating, treating For example, occlusion of patches impermeable plastic film can produce dermatophyte or candidal skin infections when fungal spores are present;1-5 yet occlusion can also improve conditions like psoriasis by affecting epidermal cell-turnover rates and by enhancing the penetration of topical medications.6.7 Occlusion is also important in epidermal wound healing,8,9 induction of miliaria, 10, 11 and secondary bacterial or

eases.

cutaneous

infection of skin lesions.12,13 The mechanisms of action are not known; nor is it known whether only one underlying mechanism is responsible for the diverse clinical effects of skin occlusion. The prevalence and severity of inflammatory Trichophyton mentagrophytes (ringworm) infections among U.S. troops in Vietnam were directly related to occlusion of the skin by wet clothing.14.11 Induction of virtually identical infections in experimentally inoculated volunteers confirmed that occlusion renders the skin susceptible to dermatophyte infections. 1, 16 Some attribute the effects of occlusion to wetness and consequent maceration of the epidermis.l,3 However, there is no evidence that wetness is the sole or even the principal factor involved, and epidemiological evidence suggests that wetness alone might even retard the development of dermatophyte infections. 14, 11 Why does occlusion seem to be necessary or important in the induction of infections in some instances (e.g., among soldiers in the tropics14,15) but not in others (e.g., among people exposed to infected animals17)? How might occlusion affect susceptibility to dermatophyte infections? Is the effect of occlusion primarily on the fungus or on the skin itself? Could knowledge of this sort be used to help prevent or treat fungal skin infections? HYPOTHESIS

Our

hypothesis

accounts

for the

major clinical, epide-

361 and laboratory features of acute ringworm infections of the glabrous skin (i.e., excluding infections of the palms, soles, and scalp). It is postulated that active infective units are produced from dermatophyte conidia and hyphae under conditions of raised CO2 tensions, and that occlusion of the skin produces the concentrations of CO2 required for such conversion. Active infective units would not require occlusion to establish infection, and hyphal elements would be less far along the path to conversion than are conidia (see accompany-

miological,

ing figure). OBSERVATIONS AND EVIDENCE

CO2 produced by Candida albihad pronounced effect on dermatophyte morphology in vitro.18 This observation and previous work’9 established that dermatophytes (T. mentagrophytes and T. rubrum) grown on agar in raised CO2 tensions produced hypersegmented hyphae and arthrospores from the normally non-segmented hyphal filaments. Arthrospores were also formed when granular cultures of T. mentagrophytes containing many microconidia and macroconidia were cultured in increased CO2 tensions.19 Arthrospores are generally found only when scrapings from active dermatophyte infections are examined microscopically." CO2 tensions at the skin surface are usually well below those required to induce arthrospore formation in vitro,21 but are raised considerably when the skin is We discovered that

cans

a

occluded with

wet

clothing,

thin ’Teflon’ sheets,

or

plastic tape.22 Occlusion by these materials produces localised susceptibility of the skin to experimental infections with dermatophyte microconidia and candidal spores.2,5 This suggests that raised CO2 tensions at the skin surface may be involved in producing susceptibility

these pathogens. Surface CO2 tensions are also increased in intertriginous and experimentally wetted skin areas;23 this corresponds with the usual distribution of dermatophyte and candidal skin infections.24 Inocula from stock cultures of T. mentagrophytes produce experimental infection in man only when occlusion is applied.l,2 This observation indicates that occlusion is essential to the infective process when hyphae or microconidia constitute the inoculum. These experimental infections appear to be directly analogous to endemic urbanl7.2S or epidemic tropical ringworm infections 14,11,26 where the involved skin surfaces have been occluded by damp clothing or footwear. Thus, the inoculum cannot produce infection in the absence of occlusion. In contrast, sporadic ruraII7,21 and laboratory-accident infections27 characteristically occur on exposed, non-occluded skin; these suggest that the inoculum is in an active infective stage at the time of contact with the skin. Both the pathogenicity and virulence of T. mentagrophytes depend on its morphological state (downy vs. granular cultures)," which can be altered in either direction by changing the environment in which the fungus is grown.28 Serial passage in laboratory animals28 or culturing under raised CO2 tensions’9 converts the relatively avirulent downy phase (composed predominately of hyphae) to the more virulent granular phase (predominately microconidia), while the reverse process occurs when microconidia are passed serially on media in the absence of CO2.28 Since arthrospore-like structures and hypersegmented hyphse are formed when inocula from granular cultures are cultured under raised CO2 tensions,18,19 it is tempting to assume that they may be even more infective than microconidia and possibly are closely related to the postulated active infective to

Life-history of a representative dermatophyte, Trichophyton mentagrophytes.

362 units. The highly infective ringworm lesions in domestic animals often show arthrospores in microscopic preparations (especially Microsporum canis infections y. 29 T. mentagrophytes infections provide the best support for the hypothesis because of their diversity and their uniquely wide epidemiological spectrum. However, support for the hypothesis is by no means limited to this

Methods and Devices DETECTION OF HEPATITIS-B SURFACE ANTIGEN IN BLOOD AND BLOOD PRODUCTS DRIED ON FILTER PAPER

organism. T. rubrum,3

T. concentricum,30 E. floccosum,31 and the yeast C. albicans4.5 produce experimental human skin infections only in the presence of occlusion, which suggests that they too require substances such as CO2 to form active infective units. Occlusion also enables T.

rubrum, usually classified

as

a

strictly human patho-

to cause experimental infections in lower animals.32 Like T. mentagrophytes, T. rubrum has a granular, sporulating morphological phase which is associated with increased virulence,33 and it can form arthrospores.24 These parallels with the hypothesised life-history and biological properties of T. mentagrophytes suggest that most if not all fungi which cause acute skin infections are similar in regard to the effects of occlusion and CO2 concentrations on their morphology, meta-

gen,"

bolism, and pathogenicity. POTENTIAL APPLICATIONS

postulated relations between occlusion of the skin, CO2 tensions, and infectivity of dermatophytes suggest ways in which ringworm infections might be prevented or controlled. Specifically, these are: (1) removal of occlusive materials from the skin; (2) application The

K. H. NOORI

H. FARZADEGAN

F. ALA Iranian National Blood

Transfusion Service,

Tehran

BLOOD-SAMPLES dried on a piece of filter paper have been used in various screening tests,I-3 but not for the detection of hepatitis-B surface antigen (HBsAg). This simple method has the following advantages: 1. Blood-samples may be obtained from newborn infants, children, anaemic patients, pregnant women, and other adults such as drug addicts or the aged, from whom it is difficult to obtain venous blood or who may refuse such a procedure. 2. Samples are dry, light, easy to post, and cannot be broken or

spilt.

,

3. Samples are easy to store; they take up little space, and remain stable for a long time. 4. The greater ease and economy of this procedure will be useful in large-scale population screening projects. Methods One drop on a

(>0.025 ml) of capillary whole blood was collected piece of filter paper (Whatman 4) from ten

circular

of substances to the skin which would interfere with the action of CO2 or would prevent its accumulation; and (3) development of clothing which would be non-occlusive when wet. The first approach has proven successful in at least one well-conducted trial,34 but its application is obviously limited. Prevention of infections by means of the second and third approaches has not yet been

attempted. Requests for reprints should be addressed to Editor, Letterman Army Institute of Research, San Francisco, California 94129, U.S.A. REFERENCES 1. 2.

Knight, A. G. J. invest. Derm. 1972, 59, 354. Reinhardt, J. H., Allen, A. M., Gunnison, D., Akers, W.

A. ibid.

1974, 63,

419. 3. Singh, G. Br. J. Derm. 1973, 89, 595. 4. Maibach, H. I., Kligman, A. M. Archs Derm. 1962, 85, 233. 5. Rebora, A., Marples, R. R., Kligman, A. M. ibid. 1973, 108, 69. 6. Fry, L., Almeyda, J., McMinn, R. Br. J. Derm. 1970, 82, 593. 7. Sulzberger, M. B., Witten, V. H. Archs Derm. 1961, 84, 1027. 8. Bothwell, J. W., Rovee, D. T. in Surgical Dressings and Wound Healing (edited by K. J. Harkiss); p. 78. London, 1971. 9. Rovee, D. T., Kurowsky, C. A., Labun, J., Downes, A. M. in Epidermal Wound Healing (edited by H. I. Maibach and D. T. Rovee); p. 159. Chicago, 1972. 10. Sulzberger, M. B., Griffin, T. B., Wiley, H. S. Dermatologica, 1967, 135, 414. 11. Stoughton, R. B. J. invest. Derm. 1964, 42, 228. 12. Marples, R. R., Kligman, A. M. in Epidermal Wound Healing (edited by H. I. Maibach and D. T. Rovee); p. 241. Chicago, 1972. 13. Leyden, J. J. Int. J. Derm. 1974, 13, 342. 14. Allen, A. M., Taplin, D. J. Am. med. Ass. 1973, 226, 864 15. Allen, A. M., Taplin, D. Proc. 3rd int. Conf. Mycoses (Scientific Publication P.A.H.O. no. 204) 1975, p. 215. 16. Allen, A. M., Reinhardt, J. H., Akers, W. A., Gunnison, D. Archs Derm.

1973, 108, 233. 17. Georg, L. K., Hand, E. A., Menges, R. A. J. invest. Derm. 1956, 27, 335. 18. King, R. D., Dillavou, C. L., Greenberg, J. H., Jeppsen, J. C., Jaeger, J. S. Can. J. Microbiol. 1976, 22, 1720. 19. Chin, B., Knight, S. G. J. gen. Microbiol. 1975, 16, 642.

Effect of storage-time (1, 3, 7, 14, and 30 days) and different elution volumes (1 and 10 ml) on results of R.I.A. (log mean c.p.m.) for HBsAg on positive capillary (and venous (---- ) blood dried on filter paper.

20. Moss, E.

S., McQuowan, A. L. Atlas of Medical Mycology, p. 195. Baltimore,

Maryland, 1962. Malten, K. E., Thiele, F. A. J. Br. J. Derm. 1973, 89, 565. King, R. D., Cunico, R. L., Maibach, H. I., Greenberg, J. H., West, M. L., Jeppsen, J. C. Acta derm.-vener., Stockh. (in the press). 23. Frame, G. W., Strauss, W. G., Maibach, H. I. J. invest. Derm. 1972, 59, 21. 22.

155. 24.

Marples, M. J. The Ecology of the Human

Skin. 1965. Georg, L. K. Ann. N.Y. Acad Sci. 1960, 89, 69. Harris, G. F. Proc. R. Soc. Med. 1962, 55, 562. Taplin, D. Personal communication. Georg, L. K. J. invest. Derm. 1954, 23, 123. Blakemore, J. C. Personal communication.

25. 26. 27. 28. 29. 30. Gonzalez-Ochoa,

p. 430. Springfield, Illinois,

A., Ricoy, E., Bravo-Becherelle, M. A. J. invest. Derm. 1964, 42, 55. 31. Sloper, J. C. ibid. 1955, 25, 21. 32. Mertz, P. M. Personal communication. 33. Wong, K. O., Chan, Y. F. Br. J. Derm. 1968, 80, 671. 34. Nickerson, W. J., Irving, L., Mehmert, H. E. Archs Derm. Syph. 1945, 52, 365.

Occlusion, carbon dioxide, and fungal skin infections.

360 trol group scores were estimated against variance between subjects, and change over time and interaction between groups over time estimated agains...
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