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TREATMENT OF PENICILLIN URTICARIA
877 in the children’s homes. She should visit the school at least once a week and be responsible for routine semi-medical tasks which now fall to the teacher, such as eye-testing; she should also keep height and weight records of the children, as well as full records of her own work. The report is packed with sensible advice about the relationship of school and parents, the introduction of the young worker to industry, the effects of urban life on children’s standards, and the purposes of education. Some examples of schools which have built up good relationships with parents make it clear that the teacher who is good at his job cannot settle down to a quiet
visiting
,
evening once he has corrected the day’s exercises. During term-time teaching is full-time work in a sense that would be accepted in few other occupations except medicine. But the teacher who gets to know the parents through parent-teacher associations, talks on educational purposes, and demonstrations by the children of music
and singing,
physical training, spoken English,
and social centre for the neighbourhood, is really interested in education, and is helping to rear young people with active minds and a grasp of social issues. This kind of work has been done too long under poor conditions. The report quotes Mr. Churchill’s remark on the plans for the new House of Commons : "We shape our buildings and afterwards our buildings shape us." Children taught in many of our present schools are having no chance of developing fully.
drama, and whose school becomes
a
"THE BIRTH OF A BABY"
IN 1940 the National Baby Welfare Council introduced country an instructional film on pregnancy and childbirth.A new generation has arisen since the film completed its tour in 1942 ; and it is once again to be released. Made in 1937 for the American Committee on Maternal Welfare, the film through the story of one woman’s pregnancy and delivery gives a fair and fairly frank account of its subject. The first aim is plainly to encourage women to seek attention early in pregnancy ; and the immediateeffect of its earlier showing was increased attendance at antenatal clinics. The film also has wise words on related topics, such as abortion; and its honesty is calculated to dispel superstitious ignorance and to foster healthy curiosity in the process of childbearing. Between 1940 and 1942 great difficulties were sttrmounted to secure a public showing of this production. The British Board of Film Censors, perhaps finding that it could not be placed in any of the three categories of approval (universal, adult, and horrific) withheld its licence. The board, contrary to popular belief, has no statutory powers or obligations ; and local authorities, though usually accepting its decisions, are not bound by them. The National Baby Welfare Council therefore approached each of the local authorities in whose area the film was to be shown. There are some 1200 authorities in this country, and many, it seems, have no suitable mechanism for dealing with such applications. Sometimes they are referred to the watch committee, sometimes to the health committee, and occasionally even to the police-court. In the end few authorities withheld their permission ; and, opinion having advanced in the last five years, it is anticipated that they will now be more ready to welcome the film. The L.C.C. has already granted it an " A " licence. Nevertheless, the position is unsatisfactory. It may be hoped that this is the forerunner of other films on kindred topics. Is the road always to be so stony ?d Clearly, as with films for entertainment, local authorities should receive at least some guide from a qualified central authority ; and perhaps the Board of Film Censors, reassured by the public’s reception of this first film, may see its way to creating an educational category. to this
1. See Lancet, 1940,
i, 325.
OLD WIVES AND GERMAN MEASLES IT has seemed odd that the old wives, always ready to find some appropriate explanation for congenital malformations,from being frightened by a dog to the more modern buzz-bombing, did not notice long ago the significance of german measles in early pregnancy. Dr. Hugh L’Etang’s letter last week (p. 849) showed that in one case a mother did connect her german measles in pregnancy with her son’s deaf-mutism, and sixty years before Gregg in Australia first suspected that the unusual number of cases of congenital cataract he was seeing in 1941 were the aftermath of the big epidemic of rubella which swept across the continent in 1939. But for that very exceptional epidemic the connexion might have remained unrecognised indefinitely, because in an ordinary epidemic year the number of cases of rubella in pregnant women would not be sufficient to produce an obvious rise in the incidence of congenital defects. The notifications in Manchester,! for instance, show that the epidemic of 1940 was remarkable for the relatively high incidence in women of child-bearing age, but if one calculates the probable number of women who were in the first three months of pregnancy at the time of their rubella-as can be done by applying the Registrar-General’s maternity incidences-it is clear that only 20 or so foetuses in Manchester were in danger from that epidemic, compared with about 14 in 1944 and less than 10 in any other year since 1940. Moreover, we do not yet know how many of these would escape damage altogether, or how many would be so severely damaged that they would be aborted or born dead. It might be practicable to obtain this information by following up the married women in the Manchester notifications (as was done in Milwaukee), but in the meantime anyone who encounters a case of miscarriage, stillbirth, or normal birth after the mother has had an exanthem early in pregnancy should report it, either in a medical journal or to the research-workers now investigating the subject for the Medical Research Council. And whenever a child is born with a congenital defect a close inquiry should be made into the events of the first few months of the mother’s pregnancy.
TREATMENT OF PENICILLIN URTICARIA PRETTY well any remedy, whether organic or inorganic, may produce sensitisation ; and the fact that penicillin occasionally does so is neither astonishing nor disappointing. Moreover, the observations of Dr. Steingold in this issue suggest that at any rate some of the sensitisation reactions are the effect of impurities rather than of penicillin itself. Though skin-tests are not a wholly reliable index of susceptibility to a drug it was a striking finding that in his 4 cases of penicillin urticaria the patients all gave positive reactions to two commercial brands of penicillin containing 1420 and 450 units per mg. but negative reactions to a " pure " preparation containing 1666 units per mg. It is conceivable that the patients were not sensitive to all forms of penicillin, and that the penicillin in the pure preparation was in a form to which they were insensitive ; but sensitivity to impurities in the commercial preparations is a far more
likely explanation.
The incidence of urticaria during penicillin therapy varies considerably, as would be expected if it is largely the result of impurities. Dawson and Hobbysaw 3 examples in 100 patients ; Pillsbury et a1.3 saw 2 in their first 200 cases of syphilis treated with penicillin but 12 in the next 200. Reactions are more common during second or subsequent courses of penicillin than during the first course, though 3 of Steingold’s 4 patients 1. Clayton-Jones, E. 2.
Lancet, Jan. 11, p. 56.
Dawson, M. H., Hobby, G. L. J. Amer. med. Ass. 1944, 124, 611. 3. Pillsbury, D. M., Steiger, H. P., Gibson, T. E. Ibid, 1947, 133, 1255.
878 urticaria in their first course. A reaction in does not necessarily indicate that the patient will get one in a subsequent course-again this is easy to understand if impurities are the cause. Skin-tests cannot be relied on to predict whether or not a patient will react to the drug. As usual with drug reactions there is an incubation period, rarely shorter than nve days but sometimes much longer, between the start of penicillin therapy and the appearance of urticaria ; in Steingold’s cases the rash appeared on the seventh or eighth day of treatment. The antihistamine drugs work very well in penicillin Tirticaria. A dose of 50-100 mg. ofBenadryl’ or ’Pyribenzamine’ three times a day will usually give relief in twelve hours, but it must be continued for as long as the rash would last without treatment or the urticaria will reappear. If the reaction is severe benadryl can be given slowly intravenously in a dosage of 5-10 mg. in 20 c.cm. of isotonic saline, but this is still rather an experimental procedure. Pillsbury et al.,mention the " decidedly startling " hypnotic effect of intravenous administration and are not convinced that it is always safe ; adrenaline seems to be as effective and its action is more predictable. As a rule they stop the penicillin immediately when a reaction appears and give benadryl or pyribenzamine 50-100 mg. t.d.s. or four-hourly by mouth. If the reaction subsides they give a test dose of 1000 units of a differentbrand of penicillin, having adrenaline at hand in case of emergency and continuing with the antihistamine drug by mouth. If there is no reaction to the test dose in six hours they give another 10,000-20,000 units, and if this is well tolerated they then return to the full dosage. The benadryl or pyribenzamine may be reduced gradually and can sometimes be given up after two or three days. Drug reactions of this kind might have been said to have lost their terrors but for one snag-that in a few people the antihistamine drugs produce sensations so unpleasant as to prohibit their use.
developed
one course
HOW TO POISON RATS
IT is obviously futile to poison bait with a substance whose taste is unacceptable to rats ; but the discovery of a poison whose taste does not offend is not the entire solution of the problem of destroying these pests. Contrary to general belief, rats are not clever at discriminating between poisoned and harmless bait ; they owe their multitudinous escapes almost entirely to their timidity. When bait is freshly laid on their runs, rats will at first give it a wide berth, even when it is not poisonous. Several days may pass before they investigate it, and even then they nibble only a very small amount. In this way, if the bait is poisoned, sublethal doses are ingested, and the discomfort that these cause only makes the rats bait-shy.1 Sublethal doses sometimes even produce tolerance, as in the case of a-naphthyl-thiourea, known to the trade as ’Antu.’2 If either shyness or tolerance results from laying a certain poison, it is better to try again, using fresh bait with a different poison. But it is still better and far more humane to prevent the development of shyness and tolerance. This is done by prebaiting : that is, by laying easily edible quantities of harmless bait in the same places for several consecutive days until the rats, suspicious of anything new, become familiar with it and eat without fear. Then by poisoning all the bait on a single occasion a kill of 85-100% of the local rat population can be confidently expected. Mass extermination is the only way to get rid of rats. Their net reproduction-rate is so high that killing a few rats occasionally is mere waste of time. .
,
Johnson, M. L., Abercrombie, M. New Biology II (Penguin Books), London, 1947). 2. See Lancet, April 12, 1947, p. 492. 1. Barnett, A. (in
The choice of poison is important from the point of view both of efficiency and of humaneness. Zinc phosphide is now generally preferred, as being highly efficient and less inhumane than most. Red squill is of unreliable quality, often ineffective, and extremely inhumane. For brown rats antu is highly toxic, with a LD 50 of : 4 mg./kg., and appears to cause relatively little pain. For the black rat, however, which is the usual host of the plague flea, its LD 50is much higher-namely, 250 mg./kg., as compared with the 40 mg./kg. of zinc phosphide and 190 mg./kg. of arsenic. MEDICAL HONOURS AMONG the honours to medical men in the Birthday Honours list those awarded for services to the State this year take precedence. Sir Godfrey Huggins, prime minister of Southern Rhodesia since 1934, becomes a privy councillor, and Surgeon Vice-Admiral H. St. Clair Colson, director-general of the Navy, a knight commander of the Bath. In the Royal Victorian order, which is reserved for personal services to the Royal House, Sir
Hugh Lett, honorary secretary to King Edward’s Hospital Fund, is appointed knight commander, while Surgeon Rear-Admiral H. E. Y. White, who accompanied the King on his tour to South Africa and has been his honorary surgeon since 1936, was promoted to the same rank. Dr. Alexander McCall, the Foreign" Secretary’s medical attendant, and Dr. T. W. Meagher, a former lord mayor of Perth, Western Australia, have become knights. Knighthoods have also been conferred on Dr. W. Norwood East for his services to the study of criminal psychology ; on Prof. D. K. Henderson, who holds the oldest chair of psychiatry in the country, that in the University of Edinburgh, and has done much to further the development of psychiatry in relation to the State ; on Prof. E. L. Kennaway, F.R.S., lately director of the Chester Beatty Research Institution of the Royal Cancer Hospital, who laid the foundations of the study of experimental carcinogenesis ; on Mr. A. H. Mclndoe, consultant in plastic surgery to the Royal Air Force, whose work on behalf of the few will be remembered by the many ; on Dr. R. A. Young, consulting physician to the Middlesex and Brompton Hospitals, who has for many years exerted a soberly progressive influence on the treatment of tuberculosis ; and on Colonel G. R. McRobert, lately professor of medicine at Madras. To these and all our other colleagues whose honours are listed on another page we offer congratulations. INTERNATIONAL CONFERENCE OF PHYSICIANS THE preliminary programme has now been published of the international conference which the Royal College of Physicians is holding in London from Sept. 8 to 18, under the presidency of Lord Moran. The work of the conference has been divided between the following
sections : cardiology (chairman, Sir Maurice Cassidy), disorders of the chest (Sir Robert Young); dermatology (Sir Archibald Gray), neurology (Dr. Gordon Holmes, F.R.s.), paediatrics (Sir Leonard Parsons), psychiatry (Dr. Bernard Hart), social medicine (Sir Wilson Jameson), and general medicine (Lord Moran). The speakers will include visitors from America, Belgium, Czechoslovakia, Denmark, France, Holland, Norway, Sweden, and Switzerland, and the full programme will be found in our advertisement columns. Dr. G. B. Mitchell-Heggs is the organising secretary of the conference, and doctors who wish to attend should apply to him for tickets of admission at the college, Pall Mall East, S.W.I.
Dr. LEONARD FINDLAY, consulting physician to the Queen Elizabeth Hospital for Children, London, and formerly professor of paediatrics in the University of at his home in Farnham 69 years of age.
Glasgow, died
was
on
June 14.
He
visiting
,
evening once he has corrected the day’s exercises. During term-time teaching is full-time work in a sense that would be accepted in few other occupations except medicine. But the teacher who gets to know the parents through parent-teacher associations, talks on educational purposes, and demonstrations by the children of music
and singing,
physical training, spoken English,
and social centre for the neighbourhood, is really interested in education, and is helping to rear young people with active minds and a grasp of social issues. This kind of work has been done too long under poor conditions. The report quotes Mr. Churchill’s remark on the plans for the new House of Commons : "We shape our buildings and afterwards our buildings shape us." Children taught in many of our present schools are having no chance of developing fully.
drama, and whose school becomes
a
"THE BIRTH OF A BABY"
IN 1940 the National Baby Welfare Council introduced country an instructional film on pregnancy and childbirth.A new generation has arisen since the film completed its tour in 1942 ; and it is once again to be released. Made in 1937 for the American Committee on Maternal Welfare, the film through the story of one woman’s pregnancy and delivery gives a fair and fairly frank account of its subject. The first aim is plainly to encourage women to seek attention early in pregnancy ; and the immediateeffect of its earlier showing was increased attendance at antenatal clinics. The film also has wise words on related topics, such as abortion; and its honesty is calculated to dispel superstitious ignorance and to foster healthy curiosity in the process of childbearing. Between 1940 and 1942 great difficulties were sttrmounted to secure a public showing of this production. The British Board of Film Censors, perhaps finding that it could not be placed in any of the three categories of approval (universal, adult, and horrific) withheld its licence. The board, contrary to popular belief, has no statutory powers or obligations ; and local authorities, though usually accepting its decisions, are not bound by them. The National Baby Welfare Council therefore approached each of the local authorities in whose area the film was to be shown. There are some 1200 authorities in this country, and many, it seems, have no suitable mechanism for dealing with such applications. Sometimes they are referred to the watch committee, sometimes to the health committee, and occasionally even to the police-court. In the end few authorities withheld their permission ; and, opinion having advanced in the last five years, it is anticipated that they will now be more ready to welcome the film. The L.C.C. has already granted it an " A " licence. Nevertheless, the position is unsatisfactory. It may be hoped that this is the forerunner of other films on kindred topics. Is the road always to be so stony ?d Clearly, as with films for entertainment, local authorities should receive at least some guide from a qualified central authority ; and perhaps the Board of Film Censors, reassured by the public’s reception of this first film, may see its way to creating an educational category. to this
1. See Lancet, 1940,
i, 325.
OLD WIVES AND GERMAN MEASLES IT has seemed odd that the old wives, always ready to find some appropriate explanation for congenital malformations,from being frightened by a dog to the more modern buzz-bombing, did not notice long ago the significance of german measles in early pregnancy. Dr. Hugh L’Etang’s letter last week (p. 849) showed that in one case a mother did connect her german measles in pregnancy with her son’s deaf-mutism, and sixty years before Gregg in Australia first suspected that the unusual number of cases of congenital cataract he was seeing in 1941 were the aftermath of the big epidemic of rubella which swept across the continent in 1939. But for that very exceptional epidemic the connexion might have remained unrecognised indefinitely, because in an ordinary epidemic year the number of cases of rubella in pregnant women would not be sufficient to produce an obvious rise in the incidence of congenital defects. The notifications in Manchester,! for instance, show that the epidemic of 1940 was remarkable for the relatively high incidence in women of child-bearing age, but if one calculates the probable number of women who were in the first three months of pregnancy at the time of their rubella-as can be done by applying the Registrar-General’s maternity incidences-it is clear that only 20 or so foetuses in Manchester were in danger from that epidemic, compared with about 14 in 1944 and less than 10 in any other year since 1940. Moreover, we do not yet know how many of these would escape damage altogether, or how many would be so severely damaged that they would be aborted or born dead. It might be practicable to obtain this information by following up the married women in the Manchester notifications (as was done in Milwaukee), but in the meantime anyone who encounters a case of miscarriage, stillbirth, or normal birth after the mother has had an exanthem early in pregnancy should report it, either in a medical journal or to the research-workers now investigating the subject for the Medical Research Council. And whenever a child is born with a congenital defect a close inquiry should be made into the events of the first few months of the mother’s pregnancy.
TREATMENT OF PENICILLIN URTICARIA PRETTY well any remedy, whether organic or inorganic, may produce sensitisation ; and the fact that penicillin occasionally does so is neither astonishing nor disappointing. Moreover, the observations of Dr. Steingold in this issue suggest that at any rate some of the sensitisation reactions are the effect of impurities rather than of penicillin itself. Though skin-tests are not a wholly reliable index of susceptibility to a drug it was a striking finding that in his 4 cases of penicillin urticaria the patients all gave positive reactions to two commercial brands of penicillin containing 1420 and 450 units per mg. but negative reactions to a " pure " preparation containing 1666 units per mg. It is conceivable that the patients were not sensitive to all forms of penicillin, and that the penicillin in the pure preparation was in a form to which they were insensitive ; but sensitivity to impurities in the commercial preparations is a far more
likely explanation.
The incidence of urticaria during penicillin therapy varies considerably, as would be expected if it is largely the result of impurities. Dawson and Hobbysaw 3 examples in 100 patients ; Pillsbury et a1.3 saw 2 in their first 200 cases of syphilis treated with penicillin but 12 in the next 200. Reactions are more common during second or subsequent courses of penicillin than during the first course, though 3 of Steingold’s 4 patients 1. Clayton-Jones, E. 2.
Lancet, Jan. 11, p. 56.
Dawson, M. H., Hobby, G. L. J. Amer. med. Ass. 1944, 124, 611. 3. Pillsbury, D. M., Steiger, H. P., Gibson, T. E. Ibid, 1947, 133, 1255.
878 urticaria in their first course. A reaction in does not necessarily indicate that the patient will get one in a subsequent course-again this is easy to understand if impurities are the cause. Skin-tests cannot be relied on to predict whether or not a patient will react to the drug. As usual with drug reactions there is an incubation period, rarely shorter than nve days but sometimes much longer, between the start of penicillin therapy and the appearance of urticaria ; in Steingold’s cases the rash appeared on the seventh or eighth day of treatment. The antihistamine drugs work very well in penicillin Tirticaria. A dose of 50-100 mg. ofBenadryl’ or ’Pyribenzamine’ three times a day will usually give relief in twelve hours, but it must be continued for as long as the rash would last without treatment or the urticaria will reappear. If the reaction is severe benadryl can be given slowly intravenously in a dosage of 5-10 mg. in 20 c.cm. of isotonic saline, but this is still rather an experimental procedure. Pillsbury et al.,mention the " decidedly startling " hypnotic effect of intravenous administration and are not convinced that it is always safe ; adrenaline seems to be as effective and its action is more predictable. As a rule they stop the penicillin immediately when a reaction appears and give benadryl or pyribenzamine 50-100 mg. t.d.s. or four-hourly by mouth. If the reaction subsides they give a test dose of 1000 units of a differentbrand of penicillin, having adrenaline at hand in case of emergency and continuing with the antihistamine drug by mouth. If there is no reaction to the test dose in six hours they give another 10,000-20,000 units, and if this is well tolerated they then return to the full dosage. The benadryl or pyribenzamine may be reduced gradually and can sometimes be given up after two or three days. Drug reactions of this kind might have been said to have lost their terrors but for one snag-that in a few people the antihistamine drugs produce sensations so unpleasant as to prohibit their use.
developed
one course
HOW TO POISON RATS
IT is obviously futile to poison bait with a substance whose taste is unacceptable to rats ; but the discovery of a poison whose taste does not offend is not the entire solution of the problem of destroying these pests. Contrary to general belief, rats are not clever at discriminating between poisoned and harmless bait ; they owe their multitudinous escapes almost entirely to their timidity. When bait is freshly laid on their runs, rats will at first give it a wide berth, even when it is not poisonous. Several days may pass before they investigate it, and even then they nibble only a very small amount. In this way, if the bait is poisoned, sublethal doses are ingested, and the discomfort that these cause only makes the rats bait-shy.1 Sublethal doses sometimes even produce tolerance, as in the case of a-naphthyl-thiourea, known to the trade as ’Antu.’2 If either shyness or tolerance results from laying a certain poison, it is better to try again, using fresh bait with a different poison. But it is still better and far more humane to prevent the development of shyness and tolerance. This is done by prebaiting : that is, by laying easily edible quantities of harmless bait in the same places for several consecutive days until the rats, suspicious of anything new, become familiar with it and eat without fear. Then by poisoning all the bait on a single occasion a kill of 85-100% of the local rat population can be confidently expected. Mass extermination is the only way to get rid of rats. Their net reproduction-rate is so high that killing a few rats occasionally is mere waste of time. .
,
Johnson, M. L., Abercrombie, M. New Biology II (Penguin Books), London, 1947). 2. See Lancet, April 12, 1947, p. 492. 1. Barnett, A. (in
The choice of poison is important from the point of view both of efficiency and of humaneness. Zinc phosphide is now generally preferred, as being highly efficient and less inhumane than most. Red squill is of unreliable quality, often ineffective, and extremely inhumane. For brown rats antu is highly toxic, with a LD 50 of : 4 mg./kg., and appears to cause relatively little pain. For the black rat, however, which is the usual host of the plague flea, its LD 50is much higher-namely, 250 mg./kg., as compared with the 40 mg./kg. of zinc phosphide and 190 mg./kg. of arsenic. MEDICAL HONOURS AMONG the honours to medical men in the Birthday Honours list those awarded for services to the State this year take precedence. Sir Godfrey Huggins, prime minister of Southern Rhodesia since 1934, becomes a privy councillor, and Surgeon Vice-Admiral H. St. Clair Colson, director-general of the Navy, a knight commander of the Bath. In the Royal Victorian order, which is reserved for personal services to the Royal House, Sir
Hugh Lett, honorary secretary to King Edward’s Hospital Fund, is appointed knight commander, while Surgeon Rear-Admiral H. E. Y. White, who accompanied the King on his tour to South Africa and has been his honorary surgeon since 1936, was promoted to the same rank. Dr. Alexander McCall, the Foreign" Secretary’s medical attendant, and Dr. T. W. Meagher, a former lord mayor of Perth, Western Australia, have become knights. Knighthoods have also been conferred on Dr. W. Norwood East for his services to the study of criminal psychology ; on Prof. D. K. Henderson, who holds the oldest chair of psychiatry in the country, that in the University of Edinburgh, and has done much to further the development of psychiatry in relation to the State ; on Prof. E. L. Kennaway, F.R.S., lately director of the Chester Beatty Research Institution of the Royal Cancer Hospital, who laid the foundations of the study of experimental carcinogenesis ; on Mr. A. H. Mclndoe, consultant in plastic surgery to the Royal Air Force, whose work on behalf of the few will be remembered by the many ; on Dr. R. A. Young, consulting physician to the Middlesex and Brompton Hospitals, who has for many years exerted a soberly progressive influence on the treatment of tuberculosis ; and on Colonel G. R. McRobert, lately professor of medicine at Madras. To these and all our other colleagues whose honours are listed on another page we offer congratulations. INTERNATIONAL CONFERENCE OF PHYSICIANS THE preliminary programme has now been published of the international conference which the Royal College of Physicians is holding in London from Sept. 8 to 18, under the presidency of Lord Moran. The work of the conference has been divided between the following
sections : cardiology (chairman, Sir Maurice Cassidy), disorders of the chest (Sir Robert Young); dermatology (Sir Archibald Gray), neurology (Dr. Gordon Holmes, F.R.s.), paediatrics (Sir Leonard Parsons), psychiatry (Dr. Bernard Hart), social medicine (Sir Wilson Jameson), and general medicine (Lord Moran). The speakers will include visitors from America, Belgium, Czechoslovakia, Denmark, France, Holland, Norway, Sweden, and Switzerland, and the full programme will be found in our advertisement columns. Dr. G. B. Mitchell-Heggs is the organising secretary of the conference, and doctors who wish to attend should apply to him for tickets of admission at the college, Pall Mall East, S.W.I.
Dr. LEONARD FINDLAY, consulting physician to the Queen Elizabeth Hospital for Children, London, and formerly professor of paediatrics in the University of at his home in Farnham 69 years of age.
Glasgow, died
was
on
June 14.
He