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SALICYLATES IN ACUTE OSTEOMYELITIS
457
sponding with date of onset, (2) typical allergic picture, (3) definite leucocytosis, (4) painlessly enlarged liver, (5) positive patch-tests, and (6) the recent description of similar cases occurring during P.A.S. therapy, it seems that this is a case of toxic hepatitis due to P.A.S. EVELYN HESS D. G. ISMAY.
Tuberculosis Unit, West Middlesex Hospital, Isleworth.
SiR,-The following
case
it
is
essentially
similar to those
described by Dr. Cuthbert and correspondents who have written since his letter appeared. The patient was a youth, aged 19, with fairly long-standing
was
better that
and, accordingly,
they should be superficial than deep ; have invariably administered these
we
antigens by the subcutaneous route. As I understand it, the present view appears to be that the injection of a foreign material into the substance of a muscle may have an irritant effect on nerve-endings and predispose them to the lodgement of poliomyelitis virus. This is, of course, hypothesis only, but it may be worth investigating. The main difficulty in this will, I think, be that in practically all cases previously inoculated the injection will have been made by the intramuscular route. We have been fortunate in escaping poliomyelitis in this area. In the past three years only five cases have come to our notice, and in only one of these was there a history of immunisation. The child concerned had received a single injection of P.T.A.P. five months before the onset of the disease ; and in his case the right leg was affected, the arms having completely escaped. ’
in the left upper lobe. The lesion was of localised endobronchitis He had been afebrile for some months and was in good general condition. On July. 15, 1950, streptomycin 1 g. daily anct P.A.S. 15 g. daily was begun. There was no diarrhoea, vomiting, or anorexia, but on the 20th day of treatment the patient J. C. SAUNDERS complained of lassitude and was found to have a temperature Cork. City Medical Officer. of 100’F. The next day he became more ill and towards the evening complained of frontal headache, shivering, and a PSEUDOMONAS AERUGINOSA "hot skin." The temperature rose to 103-5°F and the pulseSiR,—We wish to appeal for strains of Pseudomonas rate to 120 per min., but there were no other physical signs. On the 23rd day the temperature rose to 104’5°F, and simulaentginosa. 7e have carried out, with some measure taneously the patient developed a generalised papulo-ery- of success, work with a view to producing type-specific thematous rash, which began on the backs of the hands and bacteriophages capable of lysing Ps. aeruginosa. We spread from the extremities to the trunk and face. The have, however, been able to deal only with strains palms and soles escaped, and itching was confined to the latter. obtained from the West of Scotland, and we should He also complained of a severe sore throat with difficulty like, if possible, to get strains from other parts of the in swallowing ; the throat was very red and slightly cedemacountry. tous. The tongue was heavily coated. His face was flushed Any cultures sent to Professor Todd at the address and looked puffy, and there was well-marked injection of the below will be gratefully acknowledged ; and, if No were felt. given enlarged glands conjunctive. The next day he appeared extremely ill, with malaise and desired, the results of our findings will be communicated prostration ; in the evening the temperature again reached to the centre concerned. Cultures should be accom104’5OF, and the rash had become more noticeable. Up to panied by a note giving details of source and date of this time blood-counts had shown 8-12% monocytes but were isolation. otherwise normal; throat-swabs had shown no pathogens ; JAMES P. TODD School of Pharmacy, and three specimens of urine had shown no albumin, cells, or Royal Technical College, CHARLES S. TERRY. casts. No icterus developed. George Street, Glasgow, C.1. On the 25th day P.A.S. and streptomycin were discontinued. The temperature promptly fell to normal and the rash faded SALICYLATES IN ACUTE OSTEOMYELITIS within 48 hours without subsequent desquamation. Patchconnection with the article of July 29 by SiR,-In tests on Aug. 12 with 20% r.A.s., 20% sodium salicylate, and 1B11’. Konstam and Dr. Meynell, we should like to refer 20% streptomycin were all negative. There were no further to some of our well. The the Paulfindings.1 and seemed patient quite developments, We have shown in animals and in man that the effect Bunnell reaction was negative. of large doses of salicylate differs essentially from the On Aug. 21, 0’5 g. P.A.s. was given. Within 3 hours the patient complained of generalised itching and shortly after- effect of smaller doses. With large doses the body’s wards of sore throat; and the rash began to recur. There was non-specific defence mechanism is remarkably stimulated. no fever, headache, or malaise. The symptoms subsided within For this reaction adrenal activity is indispensable ; 9 hours. both adrenaline and the cortical hormones seem to take Desensitisation to P.A.s. was begun on Aug. 23 with a daily part in it. Sodium gentisate is less effective than sodium dose of 100 mg. which has been gradually increased. This has salicylate in evoking the reaction. so far been carried out uneventfully. No anti-histamine drugs Our results shed new light on Coburn’s2 observations have been used.
productive tuberculosis
cavitated, and there was evidence with slight recent deterioration.
other patients have been treated with similar doses of the same preparation of P.A.S., and other than diarrhoea and anorexia in three cases there have been no toxic reactions. Military Hospital, Cowglen, R. G. GIBBS.
Twenty-six
Glasgow.
PROPHYLACTIC INOCULATION AND POLIOMYELITIS aiR,—me present anxiety in regard to a possible connection between inoculation against diphtheria and the occurrence of poliomyelitis raises many questions. One of these concerns the method of inoculation. Practically all authorities have advocated the intramuscular route. Many years ago, when we were working with the original A.P.T. preparations of the Wellcome laboratories, we encountered sterile abscesses from time to time. These still occur, though in an insignificant proportion of cases. It has always seemed to me that while the occurrence of such abscesses remained a possibility,
on
the
therapeutic significance
of
heavy
doses of
salicy-
late ; and they again underline the importance of what has been termed the " alarm reaction " 3-namely, the non-specific reaction mediated by the A.c.T.H.-glucocorticoid mechanism. The therapeutic significance of these substances is well known.4 In some of our animal experiments salicylate was more effective than 4 mg. A.C.T.H. or ’Cortisone’ per 100 g. body-weight. Perhaps salicylate causes the release from the adrenal cortex of a different hormone. The beneficial effect of large doses of salicylate in several diseases-which so far has not been explained satisfactorily-may be also accounted for in this way. E. KELEMEN M. MAJOROS B. TANOS. Szeged University, Hungary. 1. Kelemen, E. Salicylate and Rheumatic Fever : An Experi-
mental Study. Acta med. scand. suppl. (in the press). 2. Coburn, A. F. Bull. Johns Hook. Hosp. 1943, 73, 435. 3. Selye, H. Textbook of Endocrinology. Montreal, 1947. 4. Hench, P. S., Kendall, C. E., Slocumb, C. H., Polley, H. F. Arch. intern. Med. 1950, 85, 545.
sponding with date of onset, (2) typical allergic picture, (3) definite leucocytosis, (4) painlessly enlarged liver, (5) positive patch-tests, and (6) the recent description of similar cases occurring during P.A.S. therapy, it seems that this is a case of toxic hepatitis due to P.A.S. EVELYN HESS D. G. ISMAY.
Tuberculosis Unit, West Middlesex Hospital, Isleworth.
SiR,-The following
case
it
is
essentially
similar to those
described by Dr. Cuthbert and correspondents who have written since his letter appeared. The patient was a youth, aged 19, with fairly long-standing
was
better that
and, accordingly,
they should be superficial than deep ; have invariably administered these
we
antigens by the subcutaneous route. As I understand it, the present view appears to be that the injection of a foreign material into the substance of a muscle may have an irritant effect on nerve-endings and predispose them to the lodgement of poliomyelitis virus. This is, of course, hypothesis only, but it may be worth investigating. The main difficulty in this will, I think, be that in practically all cases previously inoculated the injection will have been made by the intramuscular route. We have been fortunate in escaping poliomyelitis in this area. In the past three years only five cases have come to our notice, and in only one of these was there a history of immunisation. The child concerned had received a single injection of P.T.A.P. five months before the onset of the disease ; and in his case the right leg was affected, the arms having completely escaped. ’
in the left upper lobe. The lesion was of localised endobronchitis He had been afebrile for some months and was in good general condition. On July. 15, 1950, streptomycin 1 g. daily anct P.A.S. 15 g. daily was begun. There was no diarrhoea, vomiting, or anorexia, but on the 20th day of treatment the patient J. C. SAUNDERS complained of lassitude and was found to have a temperature Cork. City Medical Officer. of 100’F. The next day he became more ill and towards the evening complained of frontal headache, shivering, and a PSEUDOMONAS AERUGINOSA "hot skin." The temperature rose to 103-5°F and the pulseSiR,—We wish to appeal for strains of Pseudomonas rate to 120 per min., but there were no other physical signs. On the 23rd day the temperature rose to 104’5°F, and simulaentginosa. 7e have carried out, with some measure taneously the patient developed a generalised papulo-ery- of success, work with a view to producing type-specific thematous rash, which began on the backs of the hands and bacteriophages capable of lysing Ps. aeruginosa. We spread from the extremities to the trunk and face. The have, however, been able to deal only with strains palms and soles escaped, and itching was confined to the latter. obtained from the West of Scotland, and we should He also complained of a severe sore throat with difficulty like, if possible, to get strains from other parts of the in swallowing ; the throat was very red and slightly cedemacountry. tous. The tongue was heavily coated. His face was flushed Any cultures sent to Professor Todd at the address and looked puffy, and there was well-marked injection of the below will be gratefully acknowledged ; and, if No were felt. given enlarged glands conjunctive. The next day he appeared extremely ill, with malaise and desired, the results of our findings will be communicated prostration ; in the evening the temperature again reached to the centre concerned. Cultures should be accom104’5OF, and the rash had become more noticeable. Up to panied by a note giving details of source and date of this time blood-counts had shown 8-12% monocytes but were isolation. otherwise normal; throat-swabs had shown no pathogens ; JAMES P. TODD School of Pharmacy, and three specimens of urine had shown no albumin, cells, or Royal Technical College, CHARLES S. TERRY. casts. No icterus developed. George Street, Glasgow, C.1. On the 25th day P.A.S. and streptomycin were discontinued. The temperature promptly fell to normal and the rash faded SALICYLATES IN ACUTE OSTEOMYELITIS within 48 hours without subsequent desquamation. Patchconnection with the article of July 29 by SiR,-In tests on Aug. 12 with 20% r.A.s., 20% sodium salicylate, and 1B11’. Konstam and Dr. Meynell, we should like to refer 20% streptomycin were all negative. There were no further to some of our well. The the Paulfindings.1 and seemed patient quite developments, We have shown in animals and in man that the effect Bunnell reaction was negative. of large doses of salicylate differs essentially from the On Aug. 21, 0’5 g. P.A.s. was given. Within 3 hours the patient complained of generalised itching and shortly after- effect of smaller doses. With large doses the body’s wards of sore throat; and the rash began to recur. There was non-specific defence mechanism is remarkably stimulated. no fever, headache, or malaise. The symptoms subsided within For this reaction adrenal activity is indispensable ; 9 hours. both adrenaline and the cortical hormones seem to take Desensitisation to P.A.s. was begun on Aug. 23 with a daily part in it. Sodium gentisate is less effective than sodium dose of 100 mg. which has been gradually increased. This has salicylate in evoking the reaction. so far been carried out uneventfully. No anti-histamine drugs Our results shed new light on Coburn’s2 observations have been used.
productive tuberculosis
cavitated, and there was evidence with slight recent deterioration.
other patients have been treated with similar doses of the same preparation of P.A.S., and other than diarrhoea and anorexia in three cases there have been no toxic reactions. Military Hospital, Cowglen, R. G. GIBBS.
Twenty-six
Glasgow.
PROPHYLACTIC INOCULATION AND POLIOMYELITIS aiR,—me present anxiety in regard to a possible connection between inoculation against diphtheria and the occurrence of poliomyelitis raises many questions. One of these concerns the method of inoculation. Practically all authorities have advocated the intramuscular route. Many years ago, when we were working with the original A.P.T. preparations of the Wellcome laboratories, we encountered sterile abscesses from time to time. These still occur, though in an insignificant proportion of cases. It has always seemed to me that while the occurrence of such abscesses remained a possibility,
on
the
therapeutic significance
of
heavy
doses of
salicy-
late ; and they again underline the importance of what has been termed the " alarm reaction " 3-namely, the non-specific reaction mediated by the A.c.T.H.-glucocorticoid mechanism. The therapeutic significance of these substances is well known.4 In some of our animal experiments salicylate was more effective than 4 mg. A.C.T.H. or ’Cortisone’ per 100 g. body-weight. Perhaps salicylate causes the release from the adrenal cortex of a different hormone. The beneficial effect of large doses of salicylate in several diseases-which so far has not been explained satisfactorily-may be also accounted for in this way. E. KELEMEN M. MAJOROS B. TANOS. Szeged University, Hungary. 1. Kelemen, E. Salicylate and Rheumatic Fever : An Experi-
mental Study. Acta med. scand. suppl. (in the press). 2. Coburn, A. F. Bull. Johns Hook. Hosp. 1943, 73, 435. 3. Selye, H. Textbook of Endocrinology. Montreal, 1947. 4. Hench, P. S., Kendall, C. E., Slocumb, C. H., Polley, H. F. Arch. intern. Med. 1950, 85, 545.