- Email: [email protected]
MEDICINE WITHIN THE ATLANTIC COMMUNITY
561
relationship. True, the mercury was stated to have been given mostly before the onset of the illness, but this was a retrospective inquiry and the illness is not marked off by an abrupt onset. The same considerations must apply in giving value to the evidence on excretion of mercury. In the years before penicillin was produced, mercury was almost invariably given to babies with congenital syphilis, yet nobody observed acrodynia as a complication of the disease or its treatment. The finding of high cholesterol values in 3 children with symptoms of acrodynia, who had been given mercury, is interesting. Dr. Holzel and Dr. James do not state whether they found such values in other cases, and I know of no observations on this point ; but it should be well worth while to find out if a high bloodcholesterol is common either in acrodynia or after of mercury. I should like to congratulate these workers on their attempt to clear up this question of the possible significance of mercury in acrodynia, and I hope that with the large number of cases to which they have access they will continue it. My criticism may perhaps be taken in the light of Dr. Colin White’s stimulating article (in the same issue), in which he says : " Those who attack a theory are most likely to find its weaknesses ; and if it is well founded, this fact can be revealed more convincingly by the failure of critics than by the endorsement of friends."
ingestion
Children’s Department, Farnborough Hospital. Kent. Famboroush
DUNC.3N LEYS. DUNCAN JUEYS.
AN UNUSUAL EPIDEMIC
SIR,-In your annotation of Feb. 9 you mention a minor epidemic of " acute labyrinthitis " in which the main symptom was severe vertigo. In your opinion "it seems very possible that these are cases of a virus infection." I saw similar cases in the form of a minor epidemic in 1925 and of a larger one in 1934.1 The main symptoms were very severe vertigo accompanied by nausea or vomiting. In some cases hypotension and hypothermia were present. Clinical and laboratory examinations In all cases recovery was complete, were negative. mild symptoms persisted for a time. in some though Small doses of quinine and bromide seemed to have .a beneficial effect. I expressed the opinion that the disorder might be due to involvement by a neurotropic virus of the vestibular nerve or its nucleus. University of Salonica,
Greece. Greece.
G, ALEXANDRIDES. C. ALEXANDRAS.
INTRATHECAL AUREOMYCIN IN MENINGITIS
Sir,,-Where is the infection in purulent meningitis ?î Is it in the subarachnoid space, or on the surface of the brain and cord in the vascular pia mater ?î If, as I understand it, it is in the latter place, what is the point of treating meningeal infections by intrathecal antibiotics We know that they cannot pass through the pia. Are not Dr. Ainley-Walker and Dr. Bosanquet (March 1) guilty of a serious disregard of first principles ? They support their advocacy of the intrathecal route by citing four cases -of meningitis treated by local injections of aureomycin-in three cases into the subarachnoid space, and in
a fourth case into an abscess (presumably after aspiration). It is noteworthy that the fourth patient was the only survivor and the only one to be given aureomycin by the systemic route. Of the three fatalities, two were caused by secondarily infecting organisms which must have been introduced at same stage by the lumbar puncture needle. What if the cerebrospinal fluid did become sterile on culture ("although intracellular eocci were still seen in the films " in one case)’? Is not
1. Alexandrides, C.
Hellen. iatr. 1937,
no.
4.
this to be expected if a more than adequate concentration of the inhibiting antibiotic is present in the cultured fluid"1 The treatment of tetanus by the intrathecal route has long been abandoned. It is time that we ceased to put remedies into the inflammatory exudate in meningitis, and concentrated instead on efforts to get them to the causative organism through the blood-stream. County Hospital, Whiston, near Prescot.
J J. Prescot. .
M A MARTINEZ. A. MABTINEZ.
MEDICINE WITHIN THE ATLANTIC COMMUNITY
SiR,—I have read Dr. Meiklejohn’s recent papers about the United States with great interest. In the second of these (Feb. 16) he mentioned the Horse Shoe Club. As hon. secretary of this club I feel that this is an opportune moment to give some further details of what the club is attempting to achieve. This can, I think, be most concisely conveyed under a number of
headings : (A) Help
to American
,
Medical Workers
1. On short visits. Those coming to Great Britain for a few days or weeks are usually more senior members of the profession. They may be coming at the invitation of the Ciba Foundation or under the auspices of W.H.O. and other organisations. Detailed plans have usually been made for their entertainment. In addition Dr. H. A. Sandiford, of the International Medical Visitors’ Bureau at B.M.A. House, has an excellent organisation to help this type of visitor. The Horse Shoe Club can help any in this group who wish to visit particular hospitals or to contact British colleagues in their own specialty. There is also a fund available to members of the club to help to entertain these visitors. 2. On a long stay of 6-12 months. Those American doctors who are in Great Britain for long periods supported by a fellowship grant are usually younger, and may have few contacts in this country. The club is anxious to hear of this group so that it may offer them any help in making such contacts, and in entertaining them when the opportunity arises. 3. The medical services of the United States Armed Forces. The club is at present organising a scheme by which medical officers in the United States Air Force who are given one week’s study leave have an opportunity of meeting consultants in their specialty and of visiting British hospitals. If this scheme is a success it is hoped that it will be extended to the other services. 4. Proposed visits or exchanges. The club receives inquiries from the United States and tries to put the American doctor in touch with the relevant individual or organisation in Great Britain who may be able to give help. (B) Help to British Medical Workers The club feels that it can contribute most by attempting to help those of senior registrar status who wish to visit the United States as part of their training before obtaining a consultant post. It is realised that a limited number of research fellowships are granted by the Rockefeller Foundation, the Nuffield Foundation, the British Postgraduate Medical Federation, the Commonwealth Fund, and other organisations. There are also several excellent schemes of exchanges between individual hospitals. It must be recognised, however, that fellowships from a dollar source are very often arranged by personal contacts across the Atlantic. It is by this method that the club may be of assistance. We are in the process of forming an American section of the club, so that we may have more opportunity of making contacts at a large number of American medical centres. We hope that we may hear of any senior registrars who wish to visit the United States (perhaps through the registrars’ group of the B.M.A.) ; we will then do our best to help them. It should be made clear that the Horse Shoe Club acts as a kind of medical domestic agency and has no funds available for granting fellowships.
The problem of direct exchanges of doctors is more difficult. Success would depend on an agreed mechanism by which each would receive the equivalent of the other’s salary, and the position is further complicated by the present exchange regulations. The club has been investigating ways of overcoming these difficulties.
562 As
matter of interest it is estimated that a senior who is married can manage in the United States on a fellowship of$3500 per annum, taking his wife and one or even two small children with him. The club is at present a small organisation with about 80 British members (not all doctors). It is hoped that those who have visited the United States and can help in establishing contacts will get in touch with us and may be interested in joining the club. Bartholomew’,s Hospital, St. Bartholomew’s C S C. S. NICOL. N London, E.C.1. a
registrar
CANICOLA
FEVER
SiR,-In connection with your leading article on canicola fever,’ I should like to recount my experience of leptospirosis bovis treated by penicillin. In 1949 a plague of mice in the coastal zone of this country led to an epidemic of leptospirosis bovis. Up to that time this disease had been thought to be confined Dr. to workers in contact with cattle, dead or alive. Van der Hutten, director of the Israeli Government Veterinary Laboratory, informed me that the rodent plague was undoubtedly to blame, because field-mice (.Ificrotus guentheri) had been proved to be carriers. In a village of 300 adults, all agricultural workers, 47 were
affected-approximately 15% of the adult population. This during the period May-November, 1949. A blood test for leptospirosis was carried out in 32 cases, and in 25 cases it was positive for Lepto8pira bovis or L. grippo-typho8a. There is thought to be no difference between these two types of leptospira. As physician of this village I was able to give penicillin some hours after the appearance of the first symptoms (high was
’
temperature, intense headache, stiffness of the neck, blood and albumin in the urine). At this time I was giving penicillin in beeswax, 300,000 units twice daily. When the temperature had returned to normal after 24-48 hours, the dosage was reduced to 300,000 units once daily for three or four days. Of 36 cases treated in this way all reacted favourably ; but in 9 iridocyclitis occurred during the following six months. In your leading article you mention that penicillin treatment has effected a dramatic improvement in dogs, although it was proved that these were carriers up to 41/2 years later. In my experience penicillin also but rnan causes a dramatic improvement in man ; also remains a carrier, as is evident from the complication of iridocyclitis which developed up to six months after apparent cure. Nevertheless penicillin was comparatively effective, as the following observations show : 1. In most
penicillin.
the temperature rose after the first dose of patient had a temperature of 108°F four injection. This was a typical Herxheimer
rose.
3. In none of the cases treated with penicillin was jaundice Of 11 minor cases, not treated with penicillin, noticed. 5 had obvious jaundice. 4. 2 patients who were admitted to hospital for social reasons and did not receive penicillin had a high temperature for some weeks. All patients treated by me with penicillin experienced a drop in temperature after 24-48 hours. 5. At the end of the epidemic-and owing to the noticeable success of penicillin treatment-the population of the village informed me immediately of any suspected fresh cases ; so I was able to commence treatment at once. The agglutination reaction in these cases was negative. 6. In other areas of the coastal zone where penicillin treatment was, not given the cases were more severe, and a large number of patients were sent to hospital. In the
hospitals penicillin treatment opinion, to the delay of
symptoms Rishpon,
innocence. A young man, warned that they should be put out of the way of children, two nights later, merely to spite his wife, swallowed thirty of them at once and thereby took an easy flight into notoriety, which he probably would not have done had their potential danger not been pointed out to him. An old lady whom I had been trying to wean off her pheno. barbitone said rudely : "Give us some of them phoney barbitone tablets-a lot. My sister’s doctor gives her plenty, and she sends me some."
It is easy to hand out such prescriptions, but is it fair to the patient (assuming that he is not epileptic) to encourage him to be always facing the ordinary difficulties of life in a kind of barbiturate haze ? Even the rude old lady now admits that the tablets do not do her any good. Much will depend on the persistence of the patient on the one hand and on the " sales resistance" " of the doctor on the other. Bertrand Russell says : In the modern world the excess of fear above the level which may be called rational is more marked than ever before, because the habit of fear persists while the occasions for fear have greatly diminished." The subconscious fears of the recent past and the realisation that life in a world hag-ridden by wars and rumours of war is, more than ever, " nasty, brutish, and short " will no doubt make us decide to continue prescribing barbiturates ; but let us do it with some circumspection, especially when we are in the position to give the first dose. G. L. DAVIES. Brighton. TOXIC EFFECTS OF DIAMINODIPHENYLSULPHONE DIAMIN ODIPHEN
cases
One
hours after the reaction. 2. In 3 cases when the temperature had returned to normal I was compelled (owing to shortage of penicillin) to discontinue the treatment ; and after three days the temperature
in my
BARBITURATES ON THE BRAIN SIR,—I read with interest your annotation of Feb. 23. It would be interesting to know whether barbiturates are a blessing or a curse so far as the general practitioner is concerned. Hospital physicians are prone to deal out these drugs-usually the more expensive proprietary brands-with a somewhat lavish hand, and they give no indication of how long administration is to be coiitinued. The barbiturate habit is easy to acquire, and the phenobarbitone habitue can soon become to his doctor the phenobarbitone bore. Barbiturates depress many people and make them peevish and sometimes hateful to their families. Let anyone who doubts this take a few doses of phenobarbitone. To many of my patients gr. 1/2 phenobarbitone tablets are merely "’ those little things like saccharin," audsometimes it would be as well if they retained this aura of
was
not
so
effective, owing,
4-6 days between the onset of and the start of treatment.
Herzlya, Israel. Israel. near
1. Lancet,
WERNBR C’OHN. WERNER COHN. C’ORN. 1951, ii, 1169.
SIR,—We should like to comment on the article by Dr. Allday and Dr. Barnes, which appeared in your issue of Aug. 4. During the last three years we have treated over 3000 cases of leprosy with diaminodiphenylsulphone (D.A.D.P.S.) and cannot agree that it is too toxic. To take the points as they arise in the article : Dosage.—We have found that this need not exceed 0’4 g. weekly. Excellent results are obtained with this dosage, which may be safely continued for months and if necessary years with only short rest periods. Toxic effects.—There are people who are sensitive to sulphones, just as there are people sensitive to sulphonamides or aspirin or eggs ; and if given sulphones these people will produce the syndrome described (dermatitis, jaundice, &c.). In our original groups-some 350 strong, including Indians, Malays, and Chinese-we had no single case of this, but when
we
2
increased
our
numbers to about 1800 4
cases
did
acute yellow atrophy. The danger-signal of dermatitis was not recognised as such, and both received further doses of sulphone after the onset of the dermatitis. Since then, we are glad to say, there have been no fatalities in two years, though occasionally dermatitis has occurred in new cases in the period of the 8th-12th The risk of fatalities seems dose-i.e., 2nd-3rd month. to be vastly reduced by recognising this danger-signal and occur,
ending fatally with
immediately withholding sulphone.
relationship. True, the mercury was stated to have been given mostly before the onset of the illness, but this was a retrospective inquiry and the illness is not marked off by an abrupt onset. The same considerations must apply in giving value to the evidence on excretion of mercury. In the years before penicillin was produced, mercury was almost invariably given to babies with congenital syphilis, yet nobody observed acrodynia as a complication of the disease or its treatment. The finding of high cholesterol values in 3 children with symptoms of acrodynia, who had been given mercury, is interesting. Dr. Holzel and Dr. James do not state whether they found such values in other cases, and I know of no observations on this point ; but it should be well worth while to find out if a high bloodcholesterol is common either in acrodynia or after of mercury. I should like to congratulate these workers on their attempt to clear up this question of the possible significance of mercury in acrodynia, and I hope that with the large number of cases to which they have access they will continue it. My criticism may perhaps be taken in the light of Dr. Colin White’s stimulating article (in the same issue), in which he says : " Those who attack a theory are most likely to find its weaknesses ; and if it is well founded, this fact can be revealed more convincingly by the failure of critics than by the endorsement of friends."
ingestion
Children’s Department, Farnborough Hospital. Kent. Famboroush
DUNC.3N LEYS. DUNCAN JUEYS.
AN UNUSUAL EPIDEMIC
SIR,-In your annotation of Feb. 9 you mention a minor epidemic of " acute labyrinthitis " in which the main symptom was severe vertigo. In your opinion "it seems very possible that these are cases of a virus infection." I saw similar cases in the form of a minor epidemic in 1925 and of a larger one in 1934.1 The main symptoms were very severe vertigo accompanied by nausea or vomiting. In some cases hypotension and hypothermia were present. Clinical and laboratory examinations In all cases recovery was complete, were negative. mild symptoms persisted for a time. in some though Small doses of quinine and bromide seemed to have .a beneficial effect. I expressed the opinion that the disorder might be due to involvement by a neurotropic virus of the vestibular nerve or its nucleus. University of Salonica,
Greece. Greece.
G, ALEXANDRIDES. C. ALEXANDRAS.
INTRATHECAL AUREOMYCIN IN MENINGITIS
Sir,,-Where is the infection in purulent meningitis ?î Is it in the subarachnoid space, or on the surface of the brain and cord in the vascular pia mater ?î If, as I understand it, it is in the latter place, what is the point of treating meningeal infections by intrathecal antibiotics We know that they cannot pass through the pia. Are not Dr. Ainley-Walker and Dr. Bosanquet (March 1) guilty of a serious disregard of first principles ? They support their advocacy of the intrathecal route by citing four cases -of meningitis treated by local injections of aureomycin-in three cases into the subarachnoid space, and in
a fourth case into an abscess (presumably after aspiration). It is noteworthy that the fourth patient was the only survivor and the only one to be given aureomycin by the systemic route. Of the three fatalities, two were caused by secondarily infecting organisms which must have been introduced at same stage by the lumbar puncture needle. What if the cerebrospinal fluid did become sterile on culture ("although intracellular eocci were still seen in the films " in one case)’? Is not
1. Alexandrides, C.
Hellen. iatr. 1937,
no.
4.
this to be expected if a more than adequate concentration of the inhibiting antibiotic is present in the cultured fluid"1 The treatment of tetanus by the intrathecal route has long been abandoned. It is time that we ceased to put remedies into the inflammatory exudate in meningitis, and concentrated instead on efforts to get them to the causative organism through the blood-stream. County Hospital, Whiston, near Prescot.
J J. Prescot. .
M A MARTINEZ. A. MABTINEZ.
MEDICINE WITHIN THE ATLANTIC COMMUNITY
SiR,—I have read Dr. Meiklejohn’s recent papers about the United States with great interest. In the second of these (Feb. 16) he mentioned the Horse Shoe Club. As hon. secretary of this club I feel that this is an opportune moment to give some further details of what the club is attempting to achieve. This can, I think, be most concisely conveyed under a number of
headings : (A) Help
to American
,
Medical Workers
1. On short visits. Those coming to Great Britain for a few days or weeks are usually more senior members of the profession. They may be coming at the invitation of the Ciba Foundation or under the auspices of W.H.O. and other organisations. Detailed plans have usually been made for their entertainment. In addition Dr. H. A. Sandiford, of the International Medical Visitors’ Bureau at B.M.A. House, has an excellent organisation to help this type of visitor. The Horse Shoe Club can help any in this group who wish to visit particular hospitals or to contact British colleagues in their own specialty. There is also a fund available to members of the club to help to entertain these visitors. 2. On a long stay of 6-12 months. Those American doctors who are in Great Britain for long periods supported by a fellowship grant are usually younger, and may have few contacts in this country. The club is anxious to hear of this group so that it may offer them any help in making such contacts, and in entertaining them when the opportunity arises. 3. The medical services of the United States Armed Forces. The club is at present organising a scheme by which medical officers in the United States Air Force who are given one week’s study leave have an opportunity of meeting consultants in their specialty and of visiting British hospitals. If this scheme is a success it is hoped that it will be extended to the other services. 4. Proposed visits or exchanges. The club receives inquiries from the United States and tries to put the American doctor in touch with the relevant individual or organisation in Great Britain who may be able to give help. (B) Help to British Medical Workers The club feels that it can contribute most by attempting to help those of senior registrar status who wish to visit the United States as part of their training before obtaining a consultant post. It is realised that a limited number of research fellowships are granted by the Rockefeller Foundation, the Nuffield Foundation, the British Postgraduate Medical Federation, the Commonwealth Fund, and other organisations. There are also several excellent schemes of exchanges between individual hospitals. It must be recognised, however, that fellowships from a dollar source are very often arranged by personal contacts across the Atlantic. It is by this method that the club may be of assistance. We are in the process of forming an American section of the club, so that we may have more opportunity of making contacts at a large number of American medical centres. We hope that we may hear of any senior registrars who wish to visit the United States (perhaps through the registrars’ group of the B.M.A.) ; we will then do our best to help them. It should be made clear that the Horse Shoe Club acts as a kind of medical domestic agency and has no funds available for granting fellowships.
The problem of direct exchanges of doctors is more difficult. Success would depend on an agreed mechanism by which each would receive the equivalent of the other’s salary, and the position is further complicated by the present exchange regulations. The club has been investigating ways of overcoming these difficulties.
562 As
matter of interest it is estimated that a senior who is married can manage in the United States on a fellowship of$3500 per annum, taking his wife and one or even two small children with him. The club is at present a small organisation with about 80 British members (not all doctors). It is hoped that those who have visited the United States and can help in establishing contacts will get in touch with us and may be interested in joining the club. Bartholomew’,s Hospital, St. Bartholomew’s C S C. S. NICOL. N London, E.C.1. a
registrar
CANICOLA
FEVER
SiR,-In connection with your leading article on canicola fever,’ I should like to recount my experience of leptospirosis bovis treated by penicillin. In 1949 a plague of mice in the coastal zone of this country led to an epidemic of leptospirosis bovis. Up to that time this disease had been thought to be confined Dr. to workers in contact with cattle, dead or alive. Van der Hutten, director of the Israeli Government Veterinary Laboratory, informed me that the rodent plague was undoubtedly to blame, because field-mice (.Ificrotus guentheri) had been proved to be carriers. In a village of 300 adults, all agricultural workers, 47 were
affected-approximately 15% of the adult population. This during the period May-November, 1949. A blood test for leptospirosis was carried out in 32 cases, and in 25 cases it was positive for Lepto8pira bovis or L. grippo-typho8a. There is thought to be no difference between these two types of leptospira. As physician of this village I was able to give penicillin some hours after the appearance of the first symptoms (high was
’
temperature, intense headache, stiffness of the neck, blood and albumin in the urine). At this time I was giving penicillin in beeswax, 300,000 units twice daily. When the temperature had returned to normal after 24-48 hours, the dosage was reduced to 300,000 units once daily for three or four days. Of 36 cases treated in this way all reacted favourably ; but in 9 iridocyclitis occurred during the following six months. In your leading article you mention that penicillin treatment has effected a dramatic improvement in dogs, although it was proved that these were carriers up to 41/2 years later. In my experience penicillin also but rnan causes a dramatic improvement in man ; also remains a carrier, as is evident from the complication of iridocyclitis which developed up to six months after apparent cure. Nevertheless penicillin was comparatively effective, as the following observations show : 1. In most
penicillin.
the temperature rose after the first dose of patient had a temperature of 108°F four injection. This was a typical Herxheimer
rose.
3. In none of the cases treated with penicillin was jaundice Of 11 minor cases, not treated with penicillin, noticed. 5 had obvious jaundice. 4. 2 patients who were admitted to hospital for social reasons and did not receive penicillin had a high temperature for some weeks. All patients treated by me with penicillin experienced a drop in temperature after 24-48 hours. 5. At the end of the epidemic-and owing to the noticeable success of penicillin treatment-the population of the village informed me immediately of any suspected fresh cases ; so I was able to commence treatment at once. The agglutination reaction in these cases was negative. 6. In other areas of the coastal zone where penicillin treatment was, not given the cases were more severe, and a large number of patients were sent to hospital. In the
hospitals penicillin treatment opinion, to the delay of
symptoms Rishpon,
innocence. A young man, warned that they should be put out of the way of children, two nights later, merely to spite his wife, swallowed thirty of them at once and thereby took an easy flight into notoriety, which he probably would not have done had their potential danger not been pointed out to him. An old lady whom I had been trying to wean off her pheno. barbitone said rudely : "Give us some of them phoney barbitone tablets-a lot. My sister’s doctor gives her plenty, and she sends me some."
It is easy to hand out such prescriptions, but is it fair to the patient (assuming that he is not epileptic) to encourage him to be always facing the ordinary difficulties of life in a kind of barbiturate haze ? Even the rude old lady now admits that the tablets do not do her any good. Much will depend on the persistence of the patient on the one hand and on the " sales resistance" " of the doctor on the other. Bertrand Russell says : In the modern world the excess of fear above the level which may be called rational is more marked than ever before, because the habit of fear persists while the occasions for fear have greatly diminished." The subconscious fears of the recent past and the realisation that life in a world hag-ridden by wars and rumours of war is, more than ever, " nasty, brutish, and short " will no doubt make us decide to continue prescribing barbiturates ; but let us do it with some circumspection, especially when we are in the position to give the first dose. G. L. DAVIES. Brighton. TOXIC EFFECTS OF DIAMINODIPHENYLSULPHONE DIAMIN ODIPHEN
cases
One
hours after the reaction. 2. In 3 cases when the temperature had returned to normal I was compelled (owing to shortage of penicillin) to discontinue the treatment ; and after three days the temperature
in my
BARBITURATES ON THE BRAIN SIR,—I read with interest your annotation of Feb. 23. It would be interesting to know whether barbiturates are a blessing or a curse so far as the general practitioner is concerned. Hospital physicians are prone to deal out these drugs-usually the more expensive proprietary brands-with a somewhat lavish hand, and they give no indication of how long administration is to be coiitinued. The barbiturate habit is easy to acquire, and the phenobarbitone habitue can soon become to his doctor the phenobarbitone bore. Barbiturates depress many people and make them peevish and sometimes hateful to their families. Let anyone who doubts this take a few doses of phenobarbitone. To many of my patients gr. 1/2 phenobarbitone tablets are merely "’ those little things like saccharin," audsometimes it would be as well if they retained this aura of
was
not
so
effective, owing,
4-6 days between the onset of and the start of treatment.
Herzlya, Israel. Israel. near
1. Lancet,
WERNBR C’OHN. WERNER COHN. C’ORN. 1951, ii, 1169.
SIR,—We should like to comment on the article by Dr. Allday and Dr. Barnes, which appeared in your issue of Aug. 4. During the last three years we have treated over 3000 cases of leprosy with diaminodiphenylsulphone (D.A.D.P.S.) and cannot agree that it is too toxic. To take the points as they arise in the article : Dosage.—We have found that this need not exceed 0’4 g. weekly. Excellent results are obtained with this dosage, which may be safely continued for months and if necessary years with only short rest periods. Toxic effects.—There are people who are sensitive to sulphones, just as there are people sensitive to sulphonamides or aspirin or eggs ; and if given sulphones these people will produce the syndrome described (dermatitis, jaundice, &c.). In our original groups-some 350 strong, including Indians, Malays, and Chinese-we had no single case of this, but when
we
2
increased
our
numbers to about 1800 4
cases
did
acute yellow atrophy. The danger-signal of dermatitis was not recognised as such, and both received further doses of sulphone after the onset of the dermatitis. Since then, we are glad to say, there have been no fatalities in two years, though occasionally dermatitis has occurred in new cases in the period of the 8th-12th The risk of fatalities seems dose-i.e., 2nd-3rd month. to be vastly reduced by recognising this danger-signal and occur,
ending fatally with
immediately withholding sulphone.