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NEW IDEAS ON EPIDEMIC VIRUS INFECTIONS
51
small undisturbed amoebic liver necrosis yields, not inwhite or yellow pus, and it is only when the trabeculse and walls of the necrotic area have been disturbed that characteristic " anchovy " pus appears.
frequently, only
Further, by the
of
appropriate technique, such as digestion of the pus ’ Varidase ’, the proportion of amoebic abscesses " which yield amaebae is of the order of 90-100%. It will be noted that the word abscess has, to a certain extent, been avoided, in that the lesion in the liver due to invasion by the amoebx is not a true abscess, and should use
How the
amoebic liver necrosis. R. ELSDON-DEW.
COLD INJURY AMONG CHILDREN SEVERELY ILL IN THE TROPICS
SIR,-Dr. Morley’s article (Nov. 26) will, I hope, be widely read. Coldness of the extremities is so easy to appreciate in the tropics, and is still so rarely observed. Many sick children develop subnormal temperatures, but this is most typically true of kwashiorkor. " In the Gold Coast patients, coldness of the extremities was very important. Even in an equatorial climate this sign was conspicuous. Keeping the child warm was found to be one of the most important points in treatment of all the advanced
cases.
treatment
in
A radiant heat cradle would facilitate uncertain degree."1 Close contact with the mother, as Dr. Morley says, may be essential. But, failing this, a radiant-heat cradle is easy to construct wherever electricity is available, and hot-water bottles can be used where it is not. I found that with 2 or 3 of these cradles in the wards in Kumasi the results of treatment were greatly improved. I have often tried to persuade other doctors to use radiant heat for these cases, but it seems difficult to convince them that with an atmospheric temperature of 95°F or more, a sick child may be suffering from cold injury. no
American University of Beirut, Lebanon.
CICELY D. WILLIAMS.
NEW IDEAS ON EPIDEMIC VIRUS INFECTIONS
SIR,-In the matter of Dr. Garvie’s letter of Dec. 31 advocating fresh air in the treatment of influenza, may I recount another incident from the 1918 epidemic ? I was ship’s surgeon on s.s. Remuera and we had on board a battalion of New Zealand troops bound for England. After several days in Halifax where the troops went ashore and where " Spanish influenza " was present, we sailed in convoy with twenty other ships on July 20, 1918. Our epidemic started on July 23 and in the next few days we had hundreds of cases. The medical officer to the troops, a courageous young man, one Lieutenant Wishart, and I decided to bed and treat them on deck and we got the mate to screen off the starboard promenade deck. It was rather cold, there were icebergs about, and we were not popular, but, having been a patient at Frimley Sanatorium some years before where, in the spartan regime existing then, snow on the bed was a laughable triviality, I had no fears of fresh air. Whereas other ships in the convoy kept dropping out to sink their dead (whether for religious or nautical reasons I never understood), one ship losing about 30, we did not lose a man and sent only 1 to hospital when we got to Liverpool-an officer, who had been treated in his cabin-with what I now recognise to have been a mild encephalitis. Since then I have repeatedly found that when one can treat early influenza in bed in open-air conditions it is a
minor
malady without complications and little hangover. 1.
Williams,
C. D.
J. Amer. med.
Ass.
1953, 153, 1280.
membrane
uses
its birthme, but
C. G. LEAROYD.
an
Amœbiasis Research Unit, Institute for Parasitology, Durban.
mucous
it does.
HARTNUP DISEASE AND CYSTINURIA
"
preferably be known as
respiratory
right of fresh air to repel viral invaders is beyond
grateful for the favourable comments on Hartnup disease in your editorial of Dec. 24. In this article we suggested that the signs and symptoms of the condition were due to impaired transport of many monoamino-monocarboxylic aminoacids by the cells of the proximal renal tubules and by the jejunal cells. The results proved that tryptophan was poorly absorbed in the small intestine, and in addition gave suggestive but not conclusive evidence for impaired absorption of tyrosine. Transport of other aminoacids was not investigated because of the difficulties in the performance of large numbers of metabolic tests in a limited number of patients. SIR,-We
our
paper
are
on
We were originally unwilling to reject the possibility previously suggested by Nemeth and Nachmias1 of reduced action of the enzyme tryptophan pyrrolase because the patients excreted abnormally low amounts of kynurenine after oral tryptophan. This result has since been supported by Hersov and Rodnight,2who found a reduced output of kynurenic and xanthurenic acids. A dosage of tryptophan (70 mg. per kg. body-weight) was fortuitously chosen for our tests, but unfortunately at this dosage there is great variation in kynurenine excretion as related to the rate of tryptophan absorption. Since patients with Hartnup disease absorb tryptophan abnormally slowly, the experimental results are fully explained by the intestinal defect in the disease. There is thus no need to invoke deficiency of tryptophan pyrrolase. We agree that use of injected tryptophan would solve the somewhat equivocal results from administration of tryptophan by mouth. As you state, tryptamine is more likely to cause the neurological symptoms of the disease than are absorbed indolic Indole is another toxic substance formed in excess in is equally likely to cause the cerebellar ataxia present in exacerbations of the condition. Both indole and tryptamine are rapidly converted to less toxic substances by enzymes within liver cells. Tryptamine is oxidised to indolylacetic acid by monoamine oxidase, and indole to indoxyl by the non-specific enzymes of the microsomal fraction. Monamineoxidase inhibitors are therefore contraindicated in Hartnup disease, and iproniazid would be especially dangerous since it inhibits the microsomal enzyme systems in addition. These drugs might easily be prescribed to combat the psychological depression which has been a prominent feature of exacerbations of the disease. The most comprehensive modern review of Hartnup disease has now been published by Jepson and Spiro4 the former being one of the team who originally described the condition. In the last sentence of your editorial you predict that acids.
Hartnup disease, and
analogous clinical conditions to Hartnup disease will be described in the future. We, however, think they have already been described. Experiments in dogs56 suggest that aminoacids are transported by the proximal tubular cells of the kidney from the tubular lumen to the renal capillary blood in three distinct groups. These groups are: group 1, the dibasic-monocarboxylic aminoacids, lysine, ornithine, and arginine; group 2, the monoamino-monocarboxylic acids with the important exception of glycine; group 3, glycine alone. Hartnup disease is probably a 1. Nemeth, A. M., Nachmias, V. T. Science, 1960, 128, 1085. 2. Hersov, L. A., Rodnight, R. y. Neurol. Psychiat. 1960, 23, 40. 3. Brodie, B. B., Gillette, J. R., LaDu, B. N. Ann. Rev. Biochem. 1958,
27, 427.
Jepson, J. B., Spiro, M. J. The Metabolic Basis of Inherited Disease (edited by J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson). New York, 1960. 5. Beyer, K. H., Wright, L. D., Skeggs, H. R., Russo, H. F., Shaner, G. A. Amer.,7. Physiol. 1947, 151, 202. 6. Kamin, H., Handler, P. ibid. 1951, 164, 654. 4.
small undisturbed amoebic liver necrosis yields, not inwhite or yellow pus, and it is only when the trabeculse and walls of the necrotic area have been disturbed that characteristic " anchovy " pus appears.
frequently, only
Further, by the
of
appropriate technique, such as digestion of the pus ’ Varidase ’, the proportion of amoebic abscesses " which yield amaebae is of the order of 90-100%. It will be noted that the word abscess has, to a certain extent, been avoided, in that the lesion in the liver due to invasion by the amoebx is not a true abscess, and should use
How the
amoebic liver necrosis. R. ELSDON-DEW.
COLD INJURY AMONG CHILDREN SEVERELY ILL IN THE TROPICS
SIR,-Dr. Morley’s article (Nov. 26) will, I hope, be widely read. Coldness of the extremities is so easy to appreciate in the tropics, and is still so rarely observed. Many sick children develop subnormal temperatures, but this is most typically true of kwashiorkor. " In the Gold Coast patients, coldness of the extremities was very important. Even in an equatorial climate this sign was conspicuous. Keeping the child warm was found to be one of the most important points in treatment of all the advanced
cases.
treatment
in
A radiant heat cradle would facilitate uncertain degree."1 Close contact with the mother, as Dr. Morley says, may be essential. But, failing this, a radiant-heat cradle is easy to construct wherever electricity is available, and hot-water bottles can be used where it is not. I found that with 2 or 3 of these cradles in the wards in Kumasi the results of treatment were greatly improved. I have often tried to persuade other doctors to use radiant heat for these cases, but it seems difficult to convince them that with an atmospheric temperature of 95°F or more, a sick child may be suffering from cold injury. no
American University of Beirut, Lebanon.
CICELY D. WILLIAMS.
NEW IDEAS ON EPIDEMIC VIRUS INFECTIONS
SIR,-In the matter of Dr. Garvie’s letter of Dec. 31 advocating fresh air in the treatment of influenza, may I recount another incident from the 1918 epidemic ? I was ship’s surgeon on s.s. Remuera and we had on board a battalion of New Zealand troops bound for England. After several days in Halifax where the troops went ashore and where " Spanish influenza " was present, we sailed in convoy with twenty other ships on July 20, 1918. Our epidemic started on July 23 and in the next few days we had hundreds of cases. The medical officer to the troops, a courageous young man, one Lieutenant Wishart, and I decided to bed and treat them on deck and we got the mate to screen off the starboard promenade deck. It was rather cold, there were icebergs about, and we were not popular, but, having been a patient at Frimley Sanatorium some years before where, in the spartan regime existing then, snow on the bed was a laughable triviality, I had no fears of fresh air. Whereas other ships in the convoy kept dropping out to sink their dead (whether for religious or nautical reasons I never understood), one ship losing about 30, we did not lose a man and sent only 1 to hospital when we got to Liverpool-an officer, who had been treated in his cabin-with what I now recognise to have been a mild encephalitis. Since then I have repeatedly found that when one can treat early influenza in bed in open-air conditions it is a
minor
malady without complications and little hangover. 1.
Williams,
C. D.
J. Amer. med.
Ass.
1953, 153, 1280.
membrane
uses
its birthme, but
C. G. LEAROYD.
an
Amœbiasis Research Unit, Institute for Parasitology, Durban.
mucous
it does.
HARTNUP DISEASE AND CYSTINURIA
"
preferably be known as
respiratory
right of fresh air to repel viral invaders is beyond
grateful for the favourable comments on Hartnup disease in your editorial of Dec. 24. In this article we suggested that the signs and symptoms of the condition were due to impaired transport of many monoamino-monocarboxylic aminoacids by the cells of the proximal renal tubules and by the jejunal cells. The results proved that tryptophan was poorly absorbed in the small intestine, and in addition gave suggestive but not conclusive evidence for impaired absorption of tyrosine. Transport of other aminoacids was not investigated because of the difficulties in the performance of large numbers of metabolic tests in a limited number of patients. SIR,-We
our
paper
are
on
We were originally unwilling to reject the possibility previously suggested by Nemeth and Nachmias1 of reduced action of the enzyme tryptophan pyrrolase because the patients excreted abnormally low amounts of kynurenine after oral tryptophan. This result has since been supported by Hersov and Rodnight,2who found a reduced output of kynurenic and xanthurenic acids. A dosage of tryptophan (70 mg. per kg. body-weight) was fortuitously chosen for our tests, but unfortunately at this dosage there is great variation in kynurenine excretion as related to the rate of tryptophan absorption. Since patients with Hartnup disease absorb tryptophan abnormally slowly, the experimental results are fully explained by the intestinal defect in the disease. There is thus no need to invoke deficiency of tryptophan pyrrolase. We agree that use of injected tryptophan would solve the somewhat equivocal results from administration of tryptophan by mouth. As you state, tryptamine is more likely to cause the neurological symptoms of the disease than are absorbed indolic Indole is another toxic substance formed in excess in is equally likely to cause the cerebellar ataxia present in exacerbations of the condition. Both indole and tryptamine are rapidly converted to less toxic substances by enzymes within liver cells. Tryptamine is oxidised to indolylacetic acid by monoamine oxidase, and indole to indoxyl by the non-specific enzymes of the microsomal fraction. Monamineoxidase inhibitors are therefore contraindicated in Hartnup disease, and iproniazid would be especially dangerous since it inhibits the microsomal enzyme systems in addition. These drugs might easily be prescribed to combat the psychological depression which has been a prominent feature of exacerbations of the disease. The most comprehensive modern review of Hartnup disease has now been published by Jepson and Spiro4 the former being one of the team who originally described the condition. In the last sentence of your editorial you predict that acids.
Hartnup disease, and
analogous clinical conditions to Hartnup disease will be described in the future. We, however, think they have already been described. Experiments in dogs56 suggest that aminoacids are transported by the proximal tubular cells of the kidney from the tubular lumen to the renal capillary blood in three distinct groups. These groups are: group 1, the dibasic-monocarboxylic aminoacids, lysine, ornithine, and arginine; group 2, the monoamino-monocarboxylic acids with the important exception of glycine; group 3, glycine alone. Hartnup disease is probably a 1. Nemeth, A. M., Nachmias, V. T. Science, 1960, 128, 1085. 2. Hersov, L. A., Rodnight, R. y. Neurol. Psychiat. 1960, 23, 40. 3. Brodie, B. B., Gillette, J. R., LaDu, B. N. Ann. Rev. Biochem. 1958,
27, 427.
Jepson, J. B., Spiro, M. J. The Metabolic Basis of Inherited Disease (edited by J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson). New York, 1960. 5. Beyer, K. H., Wright, L. D., Skeggs, H. R., Russo, H. F., Shaner, G. A. Amer.,7. Physiol. 1947, 151, 202. 6. Kamin, H., Handler, P. ibid. 1951, 164, 654. 4.