1
1087 investigation to be attended to. One of them was indicated by Dr. J. Stevenson Logan at the Royal Society of Medicine when he described the high prevalence of paralytic attacks of poliomyelitis in school-teachers. This observation suggests an opportunity for the laboratory to help in tracing the precise path of infection in a particular school. For one thing, preventive measures could be planned more rationally if we knew whether the virus was spread by direct contact or by droplet infection. The meeting was very interested in the possible uses of gamma-globulin, but Dr. Goffe used some sobering arithmetic to support his view that gamma-globulin could be used only in small numbers of cases. Indeed, Hammon et al.,15 who described the promising gamma- globulin trials in the U.S.A., do not believe that its widespread application is practicable. 15. Hammon, W. M., Pittsburgh, P. H., Coriell, L. L., Comden, M. J., Wehrle, P. F. J. Amer. med. Ass. 1953, 151, 1272. 16. Wittkower, E. Brit. J. Derm. 1951, 63, 214. 17. Lorenz, T. H., Graham, D. T., Wolf, S. J. Lab. clin. Med. 1953, 41, 11. ACNE VULGARIS ACNE vulgaris is almost a normal accompaniment of puberty ; but if it is severe, or if it persists beyond the ’teens, then some reason has to be found. According to Wittkower 16 people with acne are arrested in their emotional and psychosexual development at the stage of puberty, with no corresponding delay in physical development : the menarche, for example, does not vary from the normal. This suggests that acne is caused by emotional disturbances connected with puberty as well as the physiological processes of maturation. Lorenz et al.,l postulating that in acne emotional influences must operate by quantitative or qualitative alterations in sebum secretion, have devised a method of collecting sebum specimens for study. They obtain their material from that sebum-rich area-the angle of the nose. The skin is first cleaned with ether so that the quantity of sebum subsequently collected represents the amount reappearing on the skin-surface in a given time. The apparatus consists of a hollow glass rod, the ground end of which is applied to the skin under p, pressure of 400 g. for 5 seconds by means of a piston- shaft with a metal sleeve at one end for holding the glass rod and with a coiled spring in its hollow handle at the other end. They find that the " control " level of facial sebum output is much the same in acne and in normal patients, and that facial sebum secretion is stable during periods of tranquility although there are day-to-day fluctuations. In patients with acne, however, sebaceous glandular function is labile, with abrupt fluctuations in facial sebum output under stressful circumstances. These patients have a labile affect, highly characteristic and stereotyped. They respond periodically with feelings of intense anger for brief periods, promptly followed by more prolonged feelings of remorse (guilt and depression), usually set up by conflict with some figure of authority, especially a parent. The daily lives of these patients are punctuated by distinct swings in affect. There is a close association between this emotional lability and fluctuations in sebum output, and the rapid phasic mood-swings are closely related to the number of facial pustules. Stressful interviews with such patients were associated with increased sebum secretion when anger was elicited, and with decreased sebum secretion when the patient responded with remorse. No significant changes in sebum secretion arose from non-stressful interviews with these patients, nor during stressful interviews in a control group of patients without acne. Lorenz and his colleagues suggest that abrupt phasic alteration in the rate of sebum secretion is an important factor in comedone formation ; stasis, inspissation, and other physiochemical changes, they say, occur in the hyposecretory phase and lead to impaction of sebum in the next hypersecretory phase, so that the acne is exacerbated after 24-48 hours. Skin-temperature may influence the viscosity of sebum and hence stasis and plug formation, and Lorenz et al. believe that the pronounced vasomotor changes associated with variations of mood may cause wide fluctuations of temperature in the skin. It is perhaps significant that acne vulgaris mainly affects the face, upper chest, and back-the blush " areas of the body. The sebaceous glands are not under direct nervous control, but they respond to endocrine stimuli. The nervous control of the sweat-glands can, however, to some extent influence the spread of sebum on the surface of the skin, hyperhidrosis leading to more emulsification and spread of the skin fat. Aron-Brunetière 18 suggests that the neuro-endocrine pathogenesis of acne is some- what as follows : a disequilibrium in the hypothalamo- pituitary mechanisms disturbs the production of pituitary gonadostimulins with the result that the balance of the steroid hormones is upset towards an excess of androgens (and, in women, progesterone) over oestrogens. Haskin et al.’ 9 have shown that in the rat the administration of progesterone produces an increase in sebaceous-gland size comparable to that induced by testosterone ; and these workers, too, suggest that adolescent acne in the female is related more to progesterone/oestrogen imbalance than to androgen/oestrogen levels.. 18. Aron-Brunetière, R. Brit. J. Derm. 1953, 65, 157. 19. Haskin, D., Lasher, N., Rothman, S. J. invest. Derm. 1953, 20, 207. 20. Lawrence, R. D., Oakley, W. Brit. med. J. 1953, i, 242. 2 1. Stowers, J. M., Nabarro, J. D. N. Proc. R. Soc. Med. (in the press). 22. Hallas-Møller, K., Petersen, K., Schlichtkrull, J. Science, 1952, 116, 394. 23. Scott, D. A., Fisher, A. M. J. Pharmacol. 1935, 55, 206. 24. Scott, D. A., Fisher, A. M. Ibid, 1936, 58, 78. NOVO ZINC INSULIN RECENT clinical trials 20 21 in this country have done much to confirm the claims of the Danish Novo Tera- peutisk Laboratories that their new insulin represents an advance on all previous insulins. Hallas-Mollerd an his colleagues 22 made the relatively simple discovery that the addition of small quantities of zinc to dissolved crystalline insulin in acetate buffer precipitated the insulin over a wide range of pH, including that of the body- fluids. This fact had previously been obscured because phosphate is sometimes used as a buffer for insulin, and added zinc is precipitated as zinc phosphate rather than combined with the insulin. There have been suggestions of an interesting relation between zinc and insulin for a long time ; for example, it was known that the pancreas contained a higher proportion of zinc than any other organ, and that the addition of large amounts of zinc to soluble insulin 23 or small amounts to protamine insulin 24 prolonged their respective actions. The Danish zinc insulin precipitate also has a long-continued action. Zinc insulin crystals form when zinc chloride is added to dissolved crystalline insulin, buffered with acetate to a pH of between 4.5 and 5-8, whereas outside this pH range the precipitate is amorphous. The fact that the zinc insulin crystals, once formed, are stable over a wide range of pH is of great practical importance. The dura- tion of the effect of these insulins depends largely on the size of the particles in the precipitate. Thus, zinc insulin crystals 100 {jL long exert a hypoglycaemio action for more than thirty hours in man, whereas the finer amorphous zinc insulin particles act for some twelve to fourteen hours. The Danes have also made up an inter- mediate variety containing both crystalline and amor- phous forms of zinc insulin, and this lasts about twenty- four hours. Each variety contains nothing but thrice

ACNE VULGARIS

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1087

investigation to be attended to. One of them wasindicated by Dr. J. Stevenson Logan at the RoyalSociety of Medicine when he described the high prevalenceof paralytic attacks of poliomyelitis in school-teachers.This observation suggests an opportunity for the

laboratory to help in tracing the precise path of infectionin a particular school. For one thing, preventive measurescould be planned more rationally if we knew whetherthe virus was spread by direct contact or by dropletinfection.The meeting was very interested in the possible uses

of gamma-globulin, but Dr. Goffe used some soberingarithmetic to support his view that gamma-globulincould be used only in small numbers of cases. Indeed,Hammon et al.,15 who described the promising gamma-globulin trials in the U.S.A., do not believe that its

widespread application is practicable.

15. Hammon, W. M., Pittsburgh, P. H., Coriell, L. L., Comden, M. J.,Wehrle, P. F. J. Amer. med. Ass. 1953, 151, 1272.

16. Wittkower, E. Brit. J. Derm. 1951, 63, 214.17. Lorenz, T. H., Graham, D. T., Wolf, S. J. Lab. clin. Med. 1953,

41, 11.

ACNE VULGARIS

ACNE vulgaris is almost a normal accompaniment ofpuberty ; but if it is severe, or if it persists beyond the’teens, then some reason has to be found. According toWittkower 16 people with acne are arrested in theiremotional and psychosexual development at the stageof puberty, with no corresponding delay in physicaldevelopment : the menarche, for example, does not

vary from the normal. This suggests that acne iscaused by emotional disturbances connected with

puberty as well as the physiological processes ofmaturation.Lorenz et al.,l postulating that in acne emotional

influences must operate by quantitative or qualitativealterations in sebum secretion, have devised a method ofcollecting sebum specimens for study. They obtaintheir material from that sebum-rich area-the angle ofthe nose. The skin is first cleaned with ether so that thequantity of sebum subsequently collected representsthe amount reappearing on the skin-surface in a giventime. The apparatus consists of a hollow glass rod, theground end of which is applied to the skin under p,pressure of 400 g. for 5 seconds by means of a piston-shaft with a metal sleeve at one end for holding theglass rod and with a coiled spring in its hollow handleat the other end. They find that the " control " levelof facial sebum output is much the same in acne andin normal patients, and that facial sebum secretion isstable during periods of tranquility although there areday-to-day fluctuations.In patients with acne, however, sebaceous glandular

function is labile, with abrupt fluctuations in facialsebum output under stressful circumstances. These

patients have a labile affect, highly characteristic andstereotyped. They respond periodically with feelingsof intense anger for brief periods, promptly followedby more prolonged feelings of remorse (guilt and

depression), usually set up by conflict with some figureof authority, especially a parent. The daily lives ofthese patients are punctuated by distinct swings inaffect. There is a close association between this emotionallability and fluctuations in sebum output, and the rapidphasic mood-swings are closely related to the numberof facial pustules. Stressful interviews with such patientswere associated with increased sebum secretion whenanger was elicited, and with decreased sebum secretionwhen the patient responded with remorse. No significantchanges in sebum secretion arose from non-stressfulinterviews with these patients, nor during stressfulinterviews in a control group of patients without acne.Lorenz and his colleagues suggest that abrupt phasicalteration in the rate of sebum secretion is an important

factor in comedone formation ; stasis, inspissation, andother physiochemical changes, they say, occur in the

hyposecretory phase and lead to impaction of sebum inthe next hypersecretory phase, so that the acne

is exacerbated after 24-48 hours. Skin-temperaturemay influence the viscosity of sebum and hence stasisand plug formation, and Lorenz et al. believe that the

pronounced vasomotor changes associated with variationsof mood may cause wide fluctuations of temperature inthe skin. It is perhaps significant that acne vulgarismainly affects the face, upper chest, and back-theblush " areas of the body.The sebaceous glands are not under direct nervous

control, but they respond to endocrine stimuli. Thenervous control of the sweat-glands can, however, tosome extent influence the spread of sebum on the surfaceof the skin, hyperhidrosis leading to more emulsificationand spread of the skin fat. Aron-Brunetière 18 suggeststhat the neuro-endocrine pathogenesis of acne is some-what as follows : a disequilibrium in the hypothalamo-pituitary mechanisms disturbs the production of pituitarygonadostimulins with the result that the balance of thesteroid hormones is upset towards an excess of androgens(and, in women, progesterone) over oestrogens. Haskinet al.’ 9 have shown that in the rat the administration of

progesterone produces an increase in sebaceous-glandsize comparable to that induced by testosterone ; andthese workers, too, suggest that adolescent acne in thefemale is related more to progesterone/oestrogen imbalancethan to androgen/oestrogen levels..

18. Aron-Brunetière, R. Brit. J. Derm. 1953, 65, 157.19. Haskin, D., Lasher, N., Rothman, S. J. invest. Derm. 1953,

20, 207.20. Lawrence, R. D., Oakley, W. Brit. med. J. 1953, i, 242.2 1. Stowers, J. M., Nabarro, J. D. N. Proc. R. Soc. Med. (in the press).22. Hallas-Møller, K., Petersen, K., Schlichtkrull, J. Science, 1952,

116, 394.23. Scott, D. A., Fisher, A. M. J. Pharmacol. 1935, 55, 206.24. Scott, D. A., Fisher, A. M. Ibid, 1936, 58, 78.

NOVO ZINC INSULIN

RECENT clinical trials 20 21 in this country have donemuch to confirm the claims of the Danish Novo Tera-peutisk Laboratories that their new insulin representsan advance on all previous insulins. Hallas-Mollerd anhis colleagues 22 made the relatively simple discovery thatthe addition of small quantities of zinc to dissolved

crystalline insulin in acetate buffer precipitated theinsulin over a wide range of pH, including that of the body-fluids. This fact had previously been obscured becausephosphate is sometimes used as a buffer for insulin, andadded zinc is precipitated as zinc phosphate ratherthan combined with the insulin. There have been

suggestions of an interesting relation between zinc andinsulin for a long time ; for example, it was known thatthe pancreas contained a higher proportion of zinc thanany other organ, and that the addition of large amountsof zinc to soluble insulin 23 or small amounts to protamineinsulin 24 prolonged their respective actions. The Danishzinc insulin precipitate also has a long-continued action.Zinc insulin crystals form when zinc chloride is addedto dissolved crystalline insulin, buffered with acetateto a pH of between 4.5 and 5-8, whereas outside this pHrange the precipitate is amorphous. The fact that thezinc insulin crystals, once formed, are stable over a widerange of pH is of great practical importance. The dura-tion of the effect of these insulins depends largely onthe size of the particles in the precipitate. Thus, zincinsulin crystals 100 {jL long exert a hypoglycaemio actionfor more than thirty hours in man, whereas the fineramorphous zinc insulin particles act for some twelve tofourteen hours. The Danes have also made up an inter-mediate variety containing both crystalline and amor-phous forms of zinc insulin, and this lasts about twenty-four hours. Each variety contains nothing but thrice