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CHEMICAL CARCINOGENS AND THEIR SIGNIFICANCE
430 visits are essential, though of little help at other times. Should agranulocytosis bediscovered, as you say, " blood-transfusion and penicillin are always advisable," but it is the antibiotics that matter and penicillin may not suffice. If within 24-48 hours the patient is not fuller antibiotic resources must be used. improving, Over previous years when treating agranulocytosis due to methvlthiouracil, we have on occasion needed to add streptomycin or aureomycin to lower the fever and arrest the infection. We trust that your gloomy statement that " if recovery is going to take place, polymorphs return to the blood within 2 to 3 days " will not suppress vigorous pursuit of adequate antibiotic treatment in such patients, for we have seen full recovery after the complete absence of polymorphs from the blood for over 12 days. Postgraduate Medical School of London. W.12.
Middlesex Hospital, London, W.1.
RUSSELL ERASER. DEBORAH DONIACH.
CLINICAL PICTURE OF SICKLE-CELL DISEASE
SiR,-Your admirable leading article of Feb. 16 on sickle-cell disease contains statements on the proportions of different haemoglobin in certain haemoglobinopathies which might mislead pathologists in their investigations should they not be familiar with the subject. In sickle-cell anaemia the red cells contain 75-100% of haemoglobin S and 0-25% of foetal haemoglobin—and not 0-25% of normal haemoglobin A. In sickle-cell/ disease the of haemoglobin-C haemoglobin S proportion is greater than that of haemoglobin C-and not about 50% each. In sickle-cell/thalassaemia the proportion of haemoglobin S may vary from 25 to 90% or more ; -but it is true to say that the condition is symptomless and not a disease " when the proportion of haemoglobin S is below 50%. In either case haemoglobin A is frequently not a small remainder" but may be present in a "
significant proportion. St. Bartholomew’s Hospital, London, E.C.1.
H. LEHMANN.
CHEMICAL CARCINOGENS AND THEIR SIGNIFICANCE
SiR,-We have read with great appreciation Dr. J. W. Cook’s succinct account last week of the present status of this subject and agree with his suggestion that the study of chemical carcinogens is likely to prove one of the most profitable forms of cancer research. There are, however, two statements which do not take into account all the experimentally proved facts, and which, carrying the authority of Dr. Cook, may give a misleading
impression. The carcinogenic hydrocarbons undoubtedly act locally at the site of direct application, but to describe this as a characteristic ignores the induction of mammary cancer by cutaneous, intranasal, intraperitoneal, and intragastric administration of methylcholanthrene, and of ovarian cancer by cutaneous treatment with dimethylbenzanthracene.1-4 The idea that the mechanism by which polycyclic " hydrocarbons transform normal cells into cancer cells is associated with their becoming firmly attached to skin proteins cannot be easily sustained in view of the finding that such protein-binding may also occur with noncarcinogenic substances of related chemical structure.56s J. W. ORR Department of Pathology, D. L. WOODHOUSE. University of Birmingham. "
J. Path. Bact. 1943, 55, 483 ; Ibid, 1946, 58, 589. 1. Orr, J. W. 2. Marchant, J., Orr, J. W., Woodhouse, D. L. Nature, Lond. 1954, 173, 307. Brit. J. Cancer, 1954, 3. Howell, J. S., Marchant, J., Orr, J. W.
8, 635.
4. Shay, H., Aegerter, E. A., Gruenstein, M., Komarov, S. A. J. nat. Cancer Inst. 1949, 10, 255. Brit. J. Cancer, 1954, 8, 346 ; Ibid, 1955, 5. Woodhouse, D. L. 9, 418. 6. Heidelberger, C., Moldenhauer, M. G. Proc. Amer. Ass. Cancer Res. 1955, 2, 24.
BIRTHDAYS OF SPASTICS
SIR,-Our experience certainly differs from that of Dr. Bevan (Feb. 16). Birthdays of the last 50 children admitted to this hospital with cerebral palsy were distributed as follows : January-March, 14; AprilJune, 3 ; July-September, 15 ; October-December, Alexandra Hospital, Luton, Bedfordshire.
18.
H. B. LEE.
TETRAETHYL LEAD POISONING
SIR,-The case described by Dr. G. L. Robinson in his letter last week is not really typical of tetraethyl lead poisoning because neither a marked anaemia nor punctate basophili a are characteristic of this form of lead poisoning, and the central nervous system is always affected. Scaling of tanks which have contained leaded petrol usually results in exposure to inorganic lead salts com. bined with other lead compounds which are the result of the breakdown of tetraethyl lead. It would seem that the brief description of this particular case is sub. stantially that of ordinary lead poisoning. It should also be mentioned that lead can always be found in the urine of normal people who have had no specific exposure, since this metal is invariably present in very small amounts in the atmosphere and food of an industrial community. Accurate methods of analysis have proved these facts. Finally I doubt very much if any case of ordinary plumbism with normal kidney function would have typical symptoms and signs unaccompanied by an excretion of lead in the urine in excess of normal. Associated Ethyl Company Medical Services,
Ltd.,
20, Berkeley Square, London, W.1.
PHILIP BOYD.
A MISSED FRACTURE
SiR,-Dr. Hunter last week suggested that my letter of Feb. 2 might be taken as " a piece of sarcasm." Although I may have rather " laid it on," what I wished to do was to draw attention once again to the difficulties confronting a junior casualty officer and to suggest that everyone should not rush to criticise him every time he made a mistake. It is time that some increased form of protection was afforded to these doctors in their work or there very soon ’won’t be any. J. F. STONE. SYPHILITIC AORTIC INCOMPETENCE are to be their excellent study of the prognosis and effects of treatment of syphilitic aortic incompetence (Feb. 2), and few people will quarrel with their main conclusions. Nevertheless their recommendation that it is probably best to give at least one full course of arsenic or bismuth to every patient, in addition to systemic penicillin. requires some comment. The figures on which this recommendation is based are, in their own words, so small that it is impossible to be certain that the results are of definite significance. This does not seem to be an reason for adequate reintroducing in the treatment of this condition highly toxic drugs such as the organic arsenicals. Severe reactions to these drugs were common, sensitivity’v frequently developed, and fatalities were far from rare. Patients with syphilitic aortitis are usually middle-aged or elderly and, in the past, proved particularly susceptible to the ill effects of this treatment. Surely, if better results are desired in the treatment of syphilitic heart-disease, it would be more reasonable to try to obtain them by increasing the dosage of penicillin up to at least 8-10 mega units, by giving a course of intramuscular bismuth, and possibly by repeating the course of penicillin on one or more occasions. I believe most physicians who have treated such patients, and all with any extensive experience of
SiR,-Dr. J. C. Leonard and Dr. W. G. Smith
congratulated
on
Middlesex Hospital, London, W.1.
RUSSELL ERASER. DEBORAH DONIACH.
CLINICAL PICTURE OF SICKLE-CELL DISEASE
SiR,-Your admirable leading article of Feb. 16 on sickle-cell disease contains statements on the proportions of different haemoglobin in certain haemoglobinopathies which might mislead pathologists in their investigations should they not be familiar with the subject. In sickle-cell anaemia the red cells contain 75-100% of haemoglobin S and 0-25% of foetal haemoglobin—and not 0-25% of normal haemoglobin A. In sickle-cell/ disease the of haemoglobin-C haemoglobin S proportion is greater than that of haemoglobin C-and not about 50% each. In sickle-cell/thalassaemia the proportion of haemoglobin S may vary from 25 to 90% or more ; -but it is true to say that the condition is symptomless and not a disease " when the proportion of haemoglobin S is below 50%. In either case haemoglobin A is frequently not a small remainder" but may be present in a "
significant proportion. St. Bartholomew’s Hospital, London, E.C.1.
H. LEHMANN.
CHEMICAL CARCINOGENS AND THEIR SIGNIFICANCE
SiR,-We have read with great appreciation Dr. J. W. Cook’s succinct account last week of the present status of this subject and agree with his suggestion that the study of chemical carcinogens is likely to prove one of the most profitable forms of cancer research. There are, however, two statements which do not take into account all the experimentally proved facts, and which, carrying the authority of Dr. Cook, may give a misleading
impression. The carcinogenic hydrocarbons undoubtedly act locally at the site of direct application, but to describe this as a characteristic ignores the induction of mammary cancer by cutaneous, intranasal, intraperitoneal, and intragastric administration of methylcholanthrene, and of ovarian cancer by cutaneous treatment with dimethylbenzanthracene.1-4 The idea that the mechanism by which polycyclic " hydrocarbons transform normal cells into cancer cells is associated with their becoming firmly attached to skin proteins cannot be easily sustained in view of the finding that such protein-binding may also occur with noncarcinogenic substances of related chemical structure.56s J. W. ORR Department of Pathology, D. L. WOODHOUSE. University of Birmingham. "
J. Path. Bact. 1943, 55, 483 ; Ibid, 1946, 58, 589. 1. Orr, J. W. 2. Marchant, J., Orr, J. W., Woodhouse, D. L. Nature, Lond. 1954, 173, 307. Brit. J. Cancer, 1954, 3. Howell, J. S., Marchant, J., Orr, J. W.
8, 635.
4. Shay, H., Aegerter, E. A., Gruenstein, M., Komarov, S. A. J. nat. Cancer Inst. 1949, 10, 255. Brit. J. Cancer, 1954, 8, 346 ; Ibid, 1955, 5. Woodhouse, D. L. 9, 418. 6. Heidelberger, C., Moldenhauer, M. G. Proc. Amer. Ass. Cancer Res. 1955, 2, 24.
BIRTHDAYS OF SPASTICS
SIR,-Our experience certainly differs from that of Dr. Bevan (Feb. 16). Birthdays of the last 50 children admitted to this hospital with cerebral palsy were distributed as follows : January-March, 14; AprilJune, 3 ; July-September, 15 ; October-December, Alexandra Hospital, Luton, Bedfordshire.
18.
H. B. LEE.
TETRAETHYL LEAD POISONING
SIR,-The case described by Dr. G. L. Robinson in his letter last week is not really typical of tetraethyl lead poisoning because neither a marked anaemia nor punctate basophili a are characteristic of this form of lead poisoning, and the central nervous system is always affected. Scaling of tanks which have contained leaded petrol usually results in exposure to inorganic lead salts com. bined with other lead compounds which are the result of the breakdown of tetraethyl lead. It would seem that the brief description of this particular case is sub. stantially that of ordinary lead poisoning. It should also be mentioned that lead can always be found in the urine of normal people who have had no specific exposure, since this metal is invariably present in very small amounts in the atmosphere and food of an industrial community. Accurate methods of analysis have proved these facts. Finally I doubt very much if any case of ordinary plumbism with normal kidney function would have typical symptoms and signs unaccompanied by an excretion of lead in the urine in excess of normal. Associated Ethyl Company Medical Services,
Ltd.,
20, Berkeley Square, London, W.1.
PHILIP BOYD.
A MISSED FRACTURE
SiR,-Dr. Hunter last week suggested that my letter of Feb. 2 might be taken as " a piece of sarcasm." Although I may have rather " laid it on," what I wished to do was to draw attention once again to the difficulties confronting a junior casualty officer and to suggest that everyone should not rush to criticise him every time he made a mistake. It is time that some increased form of protection was afforded to these doctors in their work or there very soon ’won’t be any. J. F. STONE. SYPHILITIC AORTIC INCOMPETENCE are to be their excellent study of the prognosis and effects of treatment of syphilitic aortic incompetence (Feb. 2), and few people will quarrel with their main conclusions. Nevertheless their recommendation that it is probably best to give at least one full course of arsenic or bismuth to every patient, in addition to systemic penicillin. requires some comment. The figures on which this recommendation is based are, in their own words, so small that it is impossible to be certain that the results are of definite significance. This does not seem to be an reason for adequate reintroducing in the treatment of this condition highly toxic drugs such as the organic arsenicals. Severe reactions to these drugs were common, sensitivity’v frequently developed, and fatalities were far from rare. Patients with syphilitic aortitis are usually middle-aged or elderly and, in the past, proved particularly susceptible to the ill effects of this treatment. Surely, if better results are desired in the treatment of syphilitic heart-disease, it would be more reasonable to try to obtain them by increasing the dosage of penicillin up to at least 8-10 mega units, by giving a course of intramuscular bismuth, and possibly by repeating the course of penicillin on one or more occasions. I believe most physicians who have treated such patients, and all with any extensive experience of
SiR,-Dr. J. C. Leonard and Dr. W. G. Smith
congratulated
on