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HYDROFLUMETHIAZIDE
281 any case often has to be done on the sagging mass of fibrous tissue left when regression is complete. The substances used for sclerosing veins are unsuitable, being The too toxic in the tissues. diathermy needle, insulated except for its point, is useful, but I have been afraid of injuring a nerve with it.
But I realise that a concerted
investigation of the kind I have suggested is impossible in the present fragmented state of my profession. DENIS BROWNE.
London, W.1.
SIR,-Ihave been
very inin terested the extensive correspondence on this subject, which was also debated at some length at a meeting of the Dermatological Section of the Royal Society of Medicine held at The London Hospital on June 18, 1959. My experiences conform closely to those of Dr. Simpson (Dec. 12) and I also follow Mr. Murley’s plan (Jan. 9) of showing photographs to the parents.
Some of your readers may be interested to see a series I collected in the past six years-not yet complete but very valuable for indicating to an anxious mother that Nature is on the side of recovery. The large hxmangioma has disappeared at 5 years 9 months, leaving a residual soft fleshy excess of tissue which it is anticipated will disappear within the next few years. The three blank spaces are for later photographs. Acknowledgment
is due to the
photographic department of
The
London Hospital.
BRIAN RUSSELL
London, W.1.
SiR,-In view of Dr. Simpson’s series and other
meticulously followed-up and carefully analysed series illustrating the natural history of cavernous haemangiomata, it astonishes me to find that anyone can strongly disagree, as Dr. Millington (Jan. 16) does, with these findings, which have been amply confirmed by the vast majority of dermatologists and plastic surgeons, when his sole criterion of satisfaction regarding his series of 1000 irradiated children is that " in a confined community such as this one would expect to be made aware of any untoward sequelae of treatment ". Quite apart from unhappy sequelx of irradiation, which Mr. McLaughlin (Jan. 16) so rightly deplores, Dr. Millington’s statement about " doubtful hopes of natural resolution " is in no way supported by the facts. Princess Margaret Hospital, Swindon.
SIR,-Dr. Simpson’s article the subsequent
K. D. CROW. on
strawberry nxvi and
correspondence have interested
me
greatly. I have studied 152 consecutive children with 191 strawberry nsevi, first seen between 1950 and 1953. Particular
taken to make the follow-up as comand the 9 children who were untraced plete possible, are all known to have moved away from the district. It is as
care was
unlikely that they would have done this simply to seek surgical aid. The results, which are being prepared for publication, are in complete agreement with Dr. Simpson’s and lend strong support to the view that conservative best policy.
treatment is the
Gloucestershire Royal Gloucester.
Hospital,
R. E. BOWERS.
HYDROFLUMETHIAZIDE SIR,-With great interest I read the article1 by Dr. Edmonds and Professor Wilson. A brief remark on p. 308 deserves attention because it may contribute to removing the confusion which seems to prevail regarding the conception of the kaliuretic effect of the various derivatives of chlorothiazide and its theoretical background. It reads: " Hydroflumethiazide also possesses the sulphonamide group, and probably its lack of effect on bicarbonate excretion results from the much smaller quantity used." Hydroflumethiazide and hydrochlorothiazide have a chloruretic effect which is about 15 times greater than that of chlorothiazide ; as a consequence when using them the quantity of sulphonamide supplied is about 15 times smaller than when using chlorothiazide, to obtain a certain chloruretic effect. Consequently the excretion of bicarbonate and therefore the kaliuresis are smaller. However, it is doubtful whether these differences in " the
primary kaliuretic effect " are of any therapeutic importance. Experience shows that a potassium supplement is often necessary in prolonged treatment with all existing preparations of this group of diuretics, and it is very probable that the potassium loss is more closely connected with their chloruretic effect, as is the natriuresis; whereas the kaliuresis which is connected with the inhibitory effect on carbonic anhydrase is relatively small in comparison (although it is of course the smaller the less sulphonamide they contain in proportion to their chloruretic effect). Of far greater therapeutic importance is undoubtedly " the secondary kaliuresis ", which in certain patients may arise after 1.
Lancet, 1959, ii, 303.
282 administration of all potent diuretics with natriuretic effect, and which is a consequence of the increased secretion of aldosterone initiated by the organism as a " defence " against the increased natriuresis (as well as against too rigorous restrictions of salt in the diet). Recognition of this condition, and its treatment, are only in the embryo stage, but the introduction of spirolactone opens a wide field. A great deal of unnecessary discussion as to whether one diuretic should be preferred to another, especially with
reference to the kaliuretic effect, might, however, be avoided if we (1) keep this quantitative situation of the sulphonamide group in mind, and (2) in each individual case try to establish whether the kaliuresis is primary or
secondary. TORBEN ANDERSEN
Hillerød. Denmark.
needed in the diet. Plasma levels of phenylalanine were estimated by the comparison of paper chromatograms of known standards and desalted plasma. Urine phenylpyruvicacid levels were estimated by the method of The, Fleury, and Vink.2 The results are shown in the accompanying table. Bearing in mind the fluctuations in daily urine phenyl-
was
it is seen that fructose feeding was Plasmaassociated with any marked changes. phenylalanine levels also were not affected favourably. Close observation in the ward showed that no changes in behaviour in either patient were associated with fructose feeding (Mr. Stephen Coates). Fructose feeding does not appear to have been of use in the treatment of these two patients suffering from
pyruvic-acid excretion, not
phenylpyruvic oligophrenia. We should like
FRUCTOSE TREATMENT OF PHENYLKETONURIA SIR,-Some of our patients suffering from phenylketonuric oligophrenia have not been able to keep to their low-phenylalanine diets for various reasons. Geisler and Stroderreported that they were able to increase the
tolerance and decrease the phenylketonuria of such patients by giving fructose intravenously or orally. In order to see if fructose feeding (6 g. per kg.) would help our patients we tested two known phenylketonurics who have been receiving a normal diet at home.
phenylalanine
CASE l.-A boy (H.S.C. 208562) aged 8 years was first seen the age of 21/2 years suffering from frequent fits, deafness, and mental backwardness. His general I.Q. was 20 and his plasma contained 30 mg. per 100 ml. phenylalanine and his urine contained phenylpyruvic acid. Although treatment with a low-phenylalanine diet was started and his general i.Q. rose to 30, he failed to keep to the diet and has received a normal diet for the past four years (general i.Q. now 13). CASE 2.-A girl (H.S.C. 265841) aged 5 years was first seen at the age of 2 years because of frequent fits and mental retardation. Her general I.Q. was 20, plasma-phenylalanine 30 mg. per 100 ml., and her urine contained phenylpyruvic acid. After eighteen months’ treatment with a low-phenylalanine diet the general i.Q. rose to 30 and then remained stationary when the diet was not being adhered to. For the past eight months a normal diet has been taken and the general I.Q. has fallen to 20 again. Each patient was fed on (1) a normal diet, (2) the same normal diet except that fructose 6 g. per kg. daily was substituted for all the sucrose or glucose normally taken, and (3) a normal diet again. The fructose supplied all the sugar that at
1. EFFECT
Geisler,
OF
Von E.,
FRUCTOSE
Ströder, J.
DIET
ON
Ann.
pœdiat. 1958, 191,
PLASMA-PHENYLALANINE
PHENYLPYRUVIC-ACID LEVELS
147.
AND
URINE
to
thank Mrs. M. B.
Hummerston, of the dietetic
department, Sister E. M. Baldwin, of the metabolic ward, and Mr. Stephen Coates, senior clinical psychologist, for their invaluable help in this investigation. Institute of Child Health and A. A. MONCRIEFF The Hospital for Sick Children, R. H. WILKINSON. London, W.C.1. REMOVING A SAFETY-PIN FROM THE BRONCHIAL TREE SIR,-Would I be wrong in suggesting that Chevalier Jackson demonstrated Mr. Donald Barlow’s device (Jan. 23) for removing an open safety-pin from the bronchial tree some 30 years ago ?
told in America that when Chevalier Jackson tossing open safety-pins into an anaesthetised a mild little man at the back of the room trachea, dog’s asked if he could have a go. He mastered the technique, caught the night train, and removed the open safety-pin from the trachea of his infant patient. W. HARGRAVE-WILSON. London, W.1. The story
was
was
KEROSENE (PARAFFIN) POISONING of kerosene (paraffin oil) is a common cause of accidental poisoning, particularly in children. Recent animal studies by the Medical Research Division of Esso Research and Engineering Company, Linden, New
SIR,-Ingestion
Jersey,3 have shown that kerosene poisoning is principally due to aspiration of the material into the lungs, where the kerosene produces a chemical pneumonitis. The volume of kerosene required to produce a pneumonitis is very low: thus, kerosene by aspiration into the lungs is highly dangerous. By contrast, large amounts of kerosene can be ingested without pulmonary injury or ill effect. The accompanying liquid chemicals.
table shows the oral
ORAL TOXICITY OF COMMON
toxicity of common
LIQUID CHEMICALS
If oral toxicity is low (high L.D.so) the probability of systemic intoxication is low and removal of kerosene from the stomach is unnecessary. Clinical kerosene poisoning is probably due to aspiration of a relatively small volume of kerosene during or shortly after swallowing rather than to blood-borne kerosene absorbed 2. 3.
The, T. P., Fleury, P., Vink, C. L. J. clin. chim. acta, 1957, 2, 424. Gerarde, H. W. Delaware St. med. J. 1959, 31, 276.
But I realise that a concerted
investigation of the kind I have suggested is impossible in the present fragmented state of my profession. DENIS BROWNE.
London, W.1.
SIR,-Ihave been
very inin terested the extensive correspondence on this subject, which was also debated at some length at a meeting of the Dermatological Section of the Royal Society of Medicine held at The London Hospital on June 18, 1959. My experiences conform closely to those of Dr. Simpson (Dec. 12) and I also follow Mr. Murley’s plan (Jan. 9) of showing photographs to the parents.
Some of your readers may be interested to see a series I collected in the past six years-not yet complete but very valuable for indicating to an anxious mother that Nature is on the side of recovery. The large hxmangioma has disappeared at 5 years 9 months, leaving a residual soft fleshy excess of tissue which it is anticipated will disappear within the next few years. The three blank spaces are for later photographs. Acknowledgment
is due to the
photographic department of
The
London Hospital.
BRIAN RUSSELL
London, W.1.
SiR,-In view of Dr. Simpson’s series and other
meticulously followed-up and carefully analysed series illustrating the natural history of cavernous haemangiomata, it astonishes me to find that anyone can strongly disagree, as Dr. Millington (Jan. 16) does, with these findings, which have been amply confirmed by the vast majority of dermatologists and plastic surgeons, when his sole criterion of satisfaction regarding his series of 1000 irradiated children is that " in a confined community such as this one would expect to be made aware of any untoward sequelae of treatment ". Quite apart from unhappy sequelx of irradiation, which Mr. McLaughlin (Jan. 16) so rightly deplores, Dr. Millington’s statement about " doubtful hopes of natural resolution " is in no way supported by the facts. Princess Margaret Hospital, Swindon.
SIR,-Dr. Simpson’s article the subsequent
K. D. CROW. on
strawberry nxvi and
correspondence have interested
me
greatly. I have studied 152 consecutive children with 191 strawberry nsevi, first seen between 1950 and 1953. Particular
taken to make the follow-up as comand the 9 children who were untraced plete possible, are all known to have moved away from the district. It is as
care was
unlikely that they would have done this simply to seek surgical aid. The results, which are being prepared for publication, are in complete agreement with Dr. Simpson’s and lend strong support to the view that conservative best policy.
treatment is the
Gloucestershire Royal Gloucester.
Hospital,
R. E. BOWERS.
HYDROFLUMETHIAZIDE SIR,-With great interest I read the article1 by Dr. Edmonds and Professor Wilson. A brief remark on p. 308 deserves attention because it may contribute to removing the confusion which seems to prevail regarding the conception of the kaliuretic effect of the various derivatives of chlorothiazide and its theoretical background. It reads: " Hydroflumethiazide also possesses the sulphonamide group, and probably its lack of effect on bicarbonate excretion results from the much smaller quantity used." Hydroflumethiazide and hydrochlorothiazide have a chloruretic effect which is about 15 times greater than that of chlorothiazide ; as a consequence when using them the quantity of sulphonamide supplied is about 15 times smaller than when using chlorothiazide, to obtain a certain chloruretic effect. Consequently the excretion of bicarbonate and therefore the kaliuresis are smaller. However, it is doubtful whether these differences in " the
primary kaliuretic effect " are of any therapeutic importance. Experience shows that a potassium supplement is often necessary in prolonged treatment with all existing preparations of this group of diuretics, and it is very probable that the potassium loss is more closely connected with their chloruretic effect, as is the natriuresis; whereas the kaliuresis which is connected with the inhibitory effect on carbonic anhydrase is relatively small in comparison (although it is of course the smaller the less sulphonamide they contain in proportion to their chloruretic effect). Of far greater therapeutic importance is undoubtedly " the secondary kaliuresis ", which in certain patients may arise after 1.
Lancet, 1959, ii, 303.
282 administration of all potent diuretics with natriuretic effect, and which is a consequence of the increased secretion of aldosterone initiated by the organism as a " defence " against the increased natriuresis (as well as against too rigorous restrictions of salt in the diet). Recognition of this condition, and its treatment, are only in the embryo stage, but the introduction of spirolactone opens a wide field. A great deal of unnecessary discussion as to whether one diuretic should be preferred to another, especially with
reference to the kaliuretic effect, might, however, be avoided if we (1) keep this quantitative situation of the sulphonamide group in mind, and (2) in each individual case try to establish whether the kaliuresis is primary or
secondary. TORBEN ANDERSEN
Hillerød. Denmark.
needed in the diet. Plasma levels of phenylalanine were estimated by the comparison of paper chromatograms of known standards and desalted plasma. Urine phenylpyruvicacid levels were estimated by the method of The, Fleury, and Vink.2 The results are shown in the accompanying table. Bearing in mind the fluctuations in daily urine phenyl-
was
it is seen that fructose feeding was Plasmaassociated with any marked changes. phenylalanine levels also were not affected favourably. Close observation in the ward showed that no changes in behaviour in either patient were associated with fructose feeding (Mr. Stephen Coates). Fructose feeding does not appear to have been of use in the treatment of these two patients suffering from
pyruvic-acid excretion, not
phenylpyruvic oligophrenia. We should like
FRUCTOSE TREATMENT OF PHENYLKETONURIA SIR,-Some of our patients suffering from phenylketonuric oligophrenia have not been able to keep to their low-phenylalanine diets for various reasons. Geisler and Stroderreported that they were able to increase the
tolerance and decrease the phenylketonuria of such patients by giving fructose intravenously or orally. In order to see if fructose feeding (6 g. per kg.) would help our patients we tested two known phenylketonurics who have been receiving a normal diet at home.
phenylalanine
CASE l.-A boy (H.S.C. 208562) aged 8 years was first seen the age of 21/2 years suffering from frequent fits, deafness, and mental backwardness. His general I.Q. was 20 and his plasma contained 30 mg. per 100 ml. phenylalanine and his urine contained phenylpyruvic acid. Although treatment with a low-phenylalanine diet was started and his general i.Q. rose to 30, he failed to keep to the diet and has received a normal diet for the past four years (general i.Q. now 13). CASE 2.-A girl (H.S.C. 265841) aged 5 years was first seen at the age of 2 years because of frequent fits and mental retardation. Her general I.Q. was 20, plasma-phenylalanine 30 mg. per 100 ml., and her urine contained phenylpyruvic acid. After eighteen months’ treatment with a low-phenylalanine diet the general i.Q. rose to 30 and then remained stationary when the diet was not being adhered to. For the past eight months a normal diet has been taken and the general I.Q. has fallen to 20 again. Each patient was fed on (1) a normal diet, (2) the same normal diet except that fructose 6 g. per kg. daily was substituted for all the sucrose or glucose normally taken, and (3) a normal diet again. The fructose supplied all the sugar that at
1. EFFECT
Geisler,
OF
Von E.,
FRUCTOSE
Ströder, J.
DIET
ON
Ann.
pœdiat. 1958, 191,
PLASMA-PHENYLALANINE
PHENYLPYRUVIC-ACID LEVELS
147.
AND
URINE
to
thank Mrs. M. B.
Hummerston, of the dietetic
department, Sister E. M. Baldwin, of the metabolic ward, and Mr. Stephen Coates, senior clinical psychologist, for their invaluable help in this investigation. Institute of Child Health and A. A. MONCRIEFF The Hospital for Sick Children, R. H. WILKINSON. London, W.C.1. REMOVING A SAFETY-PIN FROM THE BRONCHIAL TREE SIR,-Would I be wrong in suggesting that Chevalier Jackson demonstrated Mr. Donald Barlow’s device (Jan. 23) for removing an open safety-pin from the bronchial tree some 30 years ago ?
told in America that when Chevalier Jackson tossing open safety-pins into an anaesthetised a mild little man at the back of the room trachea, dog’s asked if he could have a go. He mastered the technique, caught the night train, and removed the open safety-pin from the trachea of his infant patient. W. HARGRAVE-WILSON. London, W.1. The story
was
was
KEROSENE (PARAFFIN) POISONING of kerosene (paraffin oil) is a common cause of accidental poisoning, particularly in children. Recent animal studies by the Medical Research Division of Esso Research and Engineering Company, Linden, New
SIR,-Ingestion
Jersey,3 have shown that kerosene poisoning is principally due to aspiration of the material into the lungs, where the kerosene produces a chemical pneumonitis. The volume of kerosene required to produce a pneumonitis is very low: thus, kerosene by aspiration into the lungs is highly dangerous. By contrast, large amounts of kerosene can be ingested without pulmonary injury or ill effect. The accompanying liquid chemicals.
table shows the oral
ORAL TOXICITY OF COMMON
toxicity of common
LIQUID CHEMICALS
If oral toxicity is low (high L.D.so) the probability of systemic intoxication is low and removal of kerosene from the stomach is unnecessary. Clinical kerosene poisoning is probably due to aspiration of a relatively small volume of kerosene during or shortly after swallowing rather than to blood-borne kerosene absorbed 2. 3.
The, T. P., Fleury, P., Vink, C. L. J. clin. chim. acta, 1957, 2, 424. Gerarde, H. W. Delaware St. med. J. 1959, 31, 276.