294 Ava. 3, 1963 ECHO. 7 VIRUS INFECTION PEA sinatra, the outbreak strains when both human and rabbit convales- ent sera were tested by neutralization tests. Oa the other hand, preliminary tests by the haemagglutination-inhibition technique using immune rabbit sera show no difference between the strains. Further work is in progress on this point, but it is possible that this difference ia the antigenic Properties of the outbreak strains may be related to their Sapacity to cause recognizable outbreaks of infection, Summary Evidence of ECHO. type 7 virus infection was demon- strated in 19 individuals in the north-east region of Scotland in 1961. Ten patients showed the clinical picture of aseptic meningitis; ECHO. type 7 virus was isolated from the cerebrospinal fluid in’ three, and in all of them antibody studies suggested concurrent infection, Neutralizing antibody tests showed antigenic differences between the outbreak strains and the prototype strain, but no differences were apparent when the haemagalutination: inhibition tests were used We should Tike to express our-thanks for permission to re to the records of cases under the cate of the fallowine rear of the stalls of Aberdeen General and Special Hosp Groups : Professor John Craig, Professor H. W. Fullerton’ H. AE. Dudley, Dr. W.' HL Galloway, Dr. Campt Murray, and Mr. W. Martin Nichols; and to'Dr. WA ke general practitioner, Laurencekirk. We ace also indebted Professor A. Macdonald for his advice and cncouragerent Reresences Bell, T. M, (1962). Scot. med. J. 7.85, Donte Stora, Hise at’ wea 2, 2. 400, Duncan 1 By. (1960) Lancer 8 as Elvin teyia, Mand Minick, J. L.°(1959). Proc. Soe. exp. B OPI 108" 6a ibn 8 Mélznder. La and Ender, 3. F. (98D. Ann. ehan, He Chick, E-'W., Doto, L La Chig, TD, Heerea, R. ag Rorolon, ML 50) Aine Oi Ok Melnick, 3-'La aad Sabin EA. (W395). te Vier aod Ricken ‘Infeciions of Man, edited by. M. Rivers Soa BL Gee 7s Pica London “Tay, L, Sad Weynants A. (1957). Amer 7, 120, 242. Sommerville, RG. add Caron, G, (1956). Lance, 2.1347, on Zeipel, Gy, ad: Svedinye, “A. (1957). rch gost Vind ee VITAMIN A IN ACNE VULGARIS RETORT BY THE SOUTH-EAST SCOTLAND FACULTY OF THE COLLEGE OF GENERAL PRACTITIONERS —rrrr——C—C Justi, oa ent exceed geen ak fiche ne sant make bed ose, 1S, TY, in ease, ou therapeu sclon me ele ere ach byt appt fo snalony sess oe i, OT 88 Plasma’ : According to Unna (1894) the basic histological picture in'cary acto a8 even hypetertsie oo ae toe which spreads fo the opeingyof the pases with the formation of cometoncr Bee ae as foes logcal picture resembles tat found in ieee An it would appear that there is some evden nese thuory tha tamin'A might be of alee a ae een of acye vans LULU ——eSe a rr ee ee 9345), who woud 100 patents wit was for pie of tix months or more bee Ua considers improvement and only hae ee Staumfiord mae the pont tht i sey ee ee aegravation ocurred: Sly ie meanest © See fmsued. Ten years ltr Pell ang Metnake rosa et experimental sport tothe theory by showing that expats of embryonic cick cctderm Btwa fe eh ees cet of vitamin A undceneay soaps ecaetn 25 compared with contol expan oes eae pte White the contol explins formed lorena ee epithelium, thove wih exe tans acing ua iteration into: musarseretngy Metta & Spits smart tha of noted alg “The largest series in which vitamin A aloes bas been used a5 therapy was detribed by enced Mesias Verbeek, and’ Van De Sie (OSS Re Htina nes tented 19 eats using 10000 10. ten eae peony ee oo. | sh tstimated the vitamin conten of th ea eeY ted found thatthe est rests wine Fea eras level rose above: 300° LU./100 mi “Taine ote tt Dr TAD, Anderson and Br EH Stake. oral administration was as satisfactory as parenteral an that doses of 50,000 LU. thrice daily were suficient t ‘achieve this level. ‘The above authors and others have ‘agreed that aco which was characterized by prominent follicular plugging i addition to the formation of comedones responded best t treatment with. vitamin A,” whereas tite results were disappointing in the pustular and cystic types. Most trial suffered from lack of proper control cases, The place of vitamin A in therapy therefore did not appear to hs to be established on firm grounds, especially as further. workers Lynch and Cook (1947) and Mj id Butterworth (1951)—found their results disappointing, It seemed that with a long-term and fluctuating condition such as acue there was a good case for a double-blind therapeutic rie, lusing an objective method of assessment to judge vessine fFurthermore, we wished to study the problems such cn Jobjective method might raise in general practice, Logan (1960), analysing the records of members of the Gollege of General Practitioners, indicated that 41 per thousand of the population sought advice for this condities annually and that most of these were in age-group 12-24 Years, which comprised 18% of the population. "A group of general practitioners would therefore be likely tock sufficient numbers for statistical purposes, and the criteria of the disease would be relatively easy to define—a very important point in any group research. Control of therapy during the trial would be simple in general practice, and the fact that there were no known cures for the conditins ‘meant that ethical objection to “inte trial using dummy tablets would be absent, [Having a large mumtee Jof observers to assess the cliNIGal picture, however, lpresented difficulties ; therefore it seemed wise to establi ls precise metlod of final assessment of results, unifor fae eases in the trial, Colous photography judged by n panel f three was {he method sclected, . Methoa ‘The trial consisted of a comparison of the effects of fablets of vitamin A, each containing 50,000 LU, ‘with [dummy tablets containing lactose 10 mg, starch 110 man3, 1963 ACNE VULGARIS Ba 295 nd tale 2-mg. Three tablets were given daily with the ‘There were thus 61 patients with & photograph taken main meal Of the day forthe period ofthe teal, andfueither ctor nor patient was awafe from appearance, tte, of mell: which tablet was. being prescribed. | The. patio ceived either the dummy ot the active tablets during be whole course of the tra. ‘Acne vulgaris was defined as a greasy skin with black cade and piles or cyte of the face] respecte vnether the condition was coafined to Tis site of not rae active dummy tablets were randomized in groups of the Gist group being allocated {o females and the second o'males, and so on aiterately to the ead of the series. rtients who agreed to participate inthe tal were selected rom the age-group 4-21 years, "Those who had had ccent xray therapy, ultraviolet light, antibiotics, or peeling, ste were excluded from the trial. The duration of the treatment was 12 weeksland patients eported at monthly intervals to their own amily doctor, rio recorded his impression ofthe progress of the condition a special card. "The nature of intercurrent illness and be treatment were recorded and a record was kept of all miients, who were excluded or who defaulted from the val, During the period of observation local therapy was sifcted to sulphurated potash and zine lotion, BAN.F. The principal method of assessment of results was by | jour photography) "A colour transparency was taken of ne Teft side of the face at the beginning and end of the rial this side sag used irespecive of the extent of the ash on the othe sie ofthe face or elsewhere oa the body. To ensure that photographic conditions were the same. on poth occasions great care was taken to use standard lighting, posure, and film. A special portrait frame was attached othe camera so-that distance and alignment were the ame forthe two photographs taken of each patient These aborate precautions were necessary 10 avoid. diferent lout depths in. the diferent transparencies «due to sterations in Tight-refection fromthe ‘face. Female patients were requested 10 avoid sing make-up before ping. photographed, and no. female. was- photographed within one week of the slart or end of her period. ‘At the end of the trial the photographs were compared| by a panel of two general practitioners: sod a consultant Jermatologist who recorded their opinions independently The photographs of each patient were identified by a sera Dumber; they were projected simultaneously from identical projectors. ont identical screens 30 that the. t¥o Photographs could be compared side by tide, There was pothing to indicate to the viewing panel which of the two pictures had been taken fist.” During the viewing session T2 pairs of photographs were shown second time to the panel in similar or reverse order on the screen without the fact being revealed to the viewers. (Further details about the equipment and techaique can be obtained from the recorders) Results ‘Twenty-four doctors participated in the trial and 80 patients attended for the first photograph. Eleven patients defaulted during the trial; 10 of these were males (seven on active tablets and three on inert tablets) and one was a female (on inert tablets). Two females were excluded from the trial, one because she was found to be over age and the second because she had been sunbathing in Greece halfway through the trial. Five patients were excluded because the photographs were faulty, and one other had to be omitted as the card was not returned. This gave 2 total of 19 patients who were excluded from the trial. before and after a three-months trial period on tablets. ‘The age and sex distribution of the sample at the beginning of the trial is given in Table I, which shows that there was a reasonably even distribution of active and dummy tablets among the different age-groups. Taste 1 ‘The panel judged improvement by reduction in the pelea ere lbp in the texture of the skin, The opinions of the panel are summarized in Table II. [Of 30 patients (15 male and 15 female) on active tabiels10 were considered to be improved ; and of 31 (16 male and 15 female) on inert tablets 11 were considered to be improved. Improvement occurred in 34% of patients and these were divided almost Tass H.—Efect of Treatment, Panel Oplnton Based’ on Photo. reply and GenratPracttoners Opinion Bae om Cine ‘Panel Opinion GPs Opinion Aises | stoic | Tee | Atle | sit | Toa [titi impos es }s )s 13 |e Mare |B Lat |B |e |e ‘equally between those taking active tablets and those taking inert ones. Deterioration occurred in 7% of those on active tablets and in 35% of those taking the inactive preparations, but the significance of this observation could be established ‘only by a larger series] There was no evidence from the ‘small numbers available that either the age or the sex of the patient affected the response to treatment. ‘The panel opinion was unanimous that seven patients had improved, eight were worse, and nine remained vunchanged. The other opinions were based on majority decisions, It is interesting that out of 12 pairs of ‘transparencies viewed for a second time the original assess- ‘ment was confirmed in nine cases. ‘The practitioners’ clinical opinions about improvement ‘or deterioration in the condition are also summarized in Table HI. Again a striking similarity was found between the response in the two groups of patients, suggesting that there is no difference between the effect brought about by vitamin A and that of the inert tablets. Record cards were available in respect of 61 patients whose photographs had been compared. Family doctors recorded improvement based on clinical impression ia 75% of the patients who were treated, whereas the panel, basing their opinion on comparative photography, recorded improvement in only 34%, of the series, Discussion It is important to try to use an_ objective method of assessing results in the treatment of a chronic skin condition such as acne, The memories of both doctor and patient cen be misleading and undue optimism is a well-known hhuman failing when a new treatment is being carried out296 Ave. 3, 1963 In this trial the point is demonstrated by the fact that improvement was recorded by general practitioners in approximately 75% of patients who completed the course, while only two patients (one on active and one on inert tablets) were reported to be worse, This is underlined when ‘one compares the opinion of the general practitioners with those of the members of the panel. However, it must be Temembered that in a condition such as acne vulgaris one has to consider the remissions and exacerbations. which Joccur as part of the disease and which are associated with such factors as sunlight and menstruation. Straumfjord (1943) listed others, such as heredity, puberty, endocrine Upset, seborrhoea, diet, digestive upset, infection, disturbance in water balance, and pyschonevrosis. The small numbers in this trial did not permit analysis of these factors, In the present trial there was no evidence that vitamin A hhad caused improvement or increased the chance of remissions that normally occur in acne from time to time, and without a double-blind trial such as this the normal fluctuations might have led to an over-optimistic opinion of benefit. In contrast, however, results did suggest that Jdeterioration was lessened by the use of this treatment, [Out of 13 people whose skin conditions were deemed 10 b2 worse at the end of the trial only two were on active tablets. This group is very small and the difference is significant only at the 2% level (x%=5.9). Furthermore, recorded results in each case were based on a majority opinion of the panel of three. It follows that it would be prudent to follow up this observation with a further tial before coming to a final conclusion, In assessing these results one should remember that some workers, such as Coombes, Saperstein, and Distelheim (1949), believe that vitamin A has to be given for at least three months before beneficial effects are noted. It may be argued that the duration of the present trial was too short, but it was felt that the onset of sunnier weather might influence the course of, the disease. This climatic factor is rarely stressed in the literature on this subject. ‘The observation that improvement occurred equally with inert and active tablets is fairly conclusive from both the clinical and the photographic evidence. We suggest, however, that photography is more acceptable as an objective. method of evaluating results than clinical impressions provided that the same routine is followed ‘carefully on each occasion, Once room-lighting, colour background, and exposure are carefully standardized, the actual photographing is brief and easy to effect. Further. more, it would be possible to resubmit the transparencies to the same or another panel to confirm the results. : Summary A double-blind trial of oral vitamin A in the treatment of | acne vulgaris is described, 150,000 LU. being given daily for 12 weeks. Colour transparencies of the left side of the face were taken before and after treatment under standard conditions, and these were used as an objective method of assessing results of treatment by a panel of three. ‘There is no evidence that vitamin A is more likely to cause improvement than inert tablets The- dangers of relying upon clinical impressions of doctor and patient to judge the value of a remedy used in \ a therapeutic trial are demonstrated, ‘The relative merits of photography and clinical impression as indices of improvement in acne vulgaris sre | discussed, ACNE VULGARIS ‘The Faculty would like to acknowledge With than advice and help given by Dr. Grant Peterkin, con dermatologist to the Royal Infirmary, Edinburgh. ‘The is also grateful to Mr. S. A. Stlaroff for statistical advi to Dr. M. Briggs, of Roche Products Limited. who provided the active and inert tablets and dodated the ‘raphic equipment. The following members and associates of the Faculty part inthe therapeutic trial: J. A. D. Anderson, 5. T. Bs E, $. Blackadder, J. D. Cruickshank, W. S. Dalgety, Flliot, 8. L. Forrest, T. Hannah, G. irvine, E. V. Kucns L Lamont, A. N. D. Large, a.'R. Laurence, J. Lipeta, MeLaren, G. McNaughton, W. W. W. MeNeih, JL. ¥ H. B. Muir, M. E. Munro, 1. M. Ross, R. E, Stewart, Stokoe, W. P, Thomson. Reritences Coombes, F.C. Saperstein, R. By and Distelbein, (196 Tae ha, ee a ell, H. Band Melby, B. (1985). J. Physol, (Lond), Gerneraad, W. F.Vashinder, Vesely Ac MT Der Sie, HR i985. ed. E Genet $9 Bish Logan, W.-P: B. (9d, Sidies on Medial and| Popeiation Hew No. 14 Sot ti. HMSO" Leadon, 4) Urmely BW, and Cook, C.D. (987). Arch. Dert. Syph. Michly’G. Ht, and Buvervorth,T, (1981). Wid, |, 4 Suaumlord, 3 'VU943). North. Med Sea) Unnge PG. (58) La J. Gets Lerbueh der dpi Togtcten natn, Seeton 8, ut So ¢ ‘tie | _ | Medical Memoranda ean Ie Alkaptonuria, Ochronosis, and “Arthritis in a Cypriot Woman | Few accounts of patients with multiple complication. chronosis exist in the Eaglsh Iterature. La Du (I in his monograph on this condition, mates a plea fos clinical reports on new cases. This paper desi further case, 1 Case Reront I The patent was a Gresk-Cypriot peasant wonisn who unsure Of her age but wae probably 6510 10 ples oe ‘ame from a sll folatedvilage in Cyprus, and had from pain and sifoes in her Knees for 20" years aod ie tack for'fve years This had caused ber to stoop and bad taken to thing a pair of malkingstcka Sie Seay relevant ondilons of consaaguty i ber family hist) She was dark-skinned, with » severe kyphosi: het hel was 5 in, (14 m) Toint movement was Citently tiie the shoulders ‘and. moderately so at the pt oad” ke Mobily of the horace and lumbar spine wi conde reduced, | Blush black pigmentation was sce, through the skin, in at cartages, nasal carlage, and the extentr teaser ot fingers. Thee was hyperkeratosis (osctbed. tothe wees walking-sticks) of the adjacent surfaces of the |thumbs a Index fingers, and this wat simian pigmented "in eck a there was a brown triangular aren to each side OF the eo Gig, 1 Black stating of ber clothing was found in eo ‘hich had been in const with alr sweat Pulse and heart sounds were normal, and these was evidence of cardiac enlargement. BP160/90. ‘A oud sey Imidsstolic quraur was probably due to articnatve calen ton Rodiology-—Heavy ealsitcston was present ia nist ef d intervertebral diss, with marked narrowing some Oak Se