- Email: [email protected]
TREATMENT OF ENURESIS
413 are irrelevant in these cases. Finally, hyperpnoea and hypocarbia may coexist in pulmonary cedema of cardiac origin,
grams
and it is reasonable to suppose that the same mechanisms are at work when these things occur in patients with oedema due to
pulmonary damage. Cardiovascular Findings The changing of the pulse with the phases of respiration and the improvement of blood-pressure wheni.p.p.R. was established were both probably related to the intrathoracic pressures, and similar changes may be seen in other circumstances. A high negative intrathoracic pressure will sometimes impede cardiac emptying during systole, and high positive pressures may enhance systolic emptying. Intra-arterial blood-pressure recording during positive-negative pressure ventilation shows swings of systolic pressure of up to 15 mm. Hg with the respiratory cycle., Rosen and Hillard have reported the deleterious effect of high intratracheal suction pressures on cardiac output.5 Patients with very laboured breathing may produce high negative intrathoracic pressures during inspiration. Tracheobronchitis Dr. Hunter also mentions the possibility that a " fibrinous tracheobronchitis " may have been in part responsible for these patients’ disabilities. While the damaged periphery of the lung may well be choked by a fibrinous exudate, we have experienced no difficulty in removing secretions by simple suction from the trachea and main bronchi whether these secretions were infected or sterile on culture. If secretions tend to block the main airways, I can only believe that this is due to inadequate humidification rather than to some cause peculiar to this type of patient. Newcastle General Hospital, Newcastle upon Tyne, 4.
M. MARSHALL.
CHEMICAL PATHOLOGIST SIR,-Your review of Techniques in Chemical Pathology (Aug. 1) refers to the author, Mr. G. A. Cheyne, F.I.M.L.T., as a chemical pathologist. To forestall perpetuation of an error which has caused controversy in the past, I write to point out that, in reference of medicine, the term " pathologist " should be applied only to the possessor of
medical
qualification. Mr. Cheyne is a highly skilled practitioner of a service ancillary to medicine but not of medicine. He should be described as a hospital " or a
"
"
clinical " biochemist but
chemical pathologist. S. C. DYKE
not as a
Chairman, Wolverhampton, Staffordshire.
Ethics and Professional Affairs Committee, Association of Clinical Pathologists.
PHENOTHIAZINE DYSKINESIA AFTER
LEUCOTOMY annotation SIR,-In your (Aug. 1) you suggest that the effect of neuronal degeneration, secondary to leucotomy, might so synergise with the chemical action of to engender chorea. No such as phenothiazines " chemical and structural synergism " is required for the development of chorea by chlordiazepoxide. A patient who came under my notice, and whose case was briefly recorded by Macleodmanifested typical chorea affecting predominantly the face, tongue and hands " after "
a
short
of treatment movements
course
involuntary treatment
was
with chlordiazepoxide. These disappeared some months after this
discontinued.
It is
perhaps significant that, of a large number of tried for the control of Huntington’s chorea, drugs Warwick and Barrowsfound chlordiazepoxide by far the most effective. SIMON BEBRMAN. BEHRMAN. London, W.1. 5. 6. 7.
Rosen, M., Hillard, E. K. Curr. Res. Anesth. Analg. 1962, 41, 50. Macleod, D. M. Lancet, 1964, i, 388. Warwick, L. H., Barrows, H. S. Bull. Los Angeles neurol. Soc. 1964, 20, 17.
HÆMODILUTION ANÆMIA ASSOCIATED WITH SIMPLE SPLENIC HYPERPLASIA SIR,-Dr. Weinstein suggests in his interesting paper (Aug. 1) that alteration in plasma oncotic pressure could account
for increased plasma-volume.
4 of his 5 patients had abnormalities in the pattern of their plasma-protein. Hsmodilution of this type can also be developed in hyperimmunised rabbits with very high serumgammaglobulin levels,l-3 and McCance and Widdowson4 have shown that newborn piglets receiving colostrum exhibit an increase in serum-gammaglobulin and plasma-volume. It would be interesting to know the plasma-cell concen-
tration in bone-marrow and spleen and the serum-electrophoresis in Dr. Weinstein’s cases 1-4. Medical Department B,
Bispebjerg Hospital, Copenhagen.
M.
BJØRNEBOE.
TREATMENT OF ENURESIS
SIR,-I, too, was horrified at the treatments for enuresis mentioned in your leading article, and in the subsequent letters. Dr. Murray (Aug. 15) says that enuretic children " pass abnormally large quantities of urine during the night and on rising ". Some time ago I measured the urine passed by some enuretic teenagers, and found that the amount of urine passed first thing in the morning averaged 5 oz. in 226 measurings. In one boy, it was never more than 3 oz. whether his bed was wet or dry. It takes very little fluid to soak a bed, as anyone will know if they have ever upset a cup of tea. During an investigation of the intake/output of pregnant women5 it was found that those women who had to pass urine several times in the night, passed (in a 24-hour period) less than those who had no nocturia. Reducing the fluid intake helped neither the pregnant women with nocturia nor the teenagers with enuresis. I agree with Dr. Gutierrez that the cause of enuresis has something to do with the nervous system, although psychotherapy has not improved any of my teenagers. The trouble seems to be physiological rather than psychological. In the above-mentioned investigation, it was found that nocturia could be cured in pregnant women. The same treatment was given to teenager enuretics, and the number of wet beds per week was reduced, but so far a complete cure has not been obtained. The teenagers also became conscious of wanting to pass water in the night, and, for the first time in their lives, they woke up and passed water. Strangely enough, their beds were dry on the nights that they did not wake up and pass water. Work on the physiology of nerves might possibly lead to a better understanding of enuresis. The condition may also have something to do with growth, or the growth hormone, as spontaneous cure of nocturia in women usually occurs after the birth of the baby; and spontaneous cure of enuresis in children usually occurs during periods of little growth or at the end of adolescence when growth has ceased. Derby.
MARGARET ROBINSON.
SIR,-Ifail to see why Sir Francis Walshe should have been so depressed by your leading article of June 27; for it described a method which brings complete, or almost complete, relief to about 75% of persistent enuretics. In his bookhe refers to the " frequent failure of routine lines of treatment ... now available "; but, now that he is aware of the success of the buzzer, one would have expected him to be as delighted as are the many patients who have been cured by it. ...
Bjørneboe, M., Schwartz, M. J. exp. Med. 1959, 110, 259. Bjørneboe, M., Jarnum, S. ibid. 1961, 113, 1005. Rotschild, M. A., Oratz, M., Franklin, E. E., Schreiber, S. S. J. clin. Invest. 1962, 41, 1564. 4. McCance, R. A., Widdowson, E. M. J. Physiol. 1959, 145, 547. 5. Robinson, M. Med. Offr, 1964, 111, 75. 6. Diseases of the Nervous System 5th ed. (1947), p. 299; 9th ed. (1958), p. 328.
1. 2. 3.
414 Sir Francis goes so far as to describe an apparatus being similar to a front-door bell as a " barbarous contraption "; yet he was quite prepared to recommend strychnine and belladonna for this complaint in the earlier editions of his book, though (significantly) these have been changed for less dangerous drugs in the latest edition. Can anyone explain why some doctors react so violently and irrationally against the buzzer, yet appear to have no qualms in recommending the use of potentially lethal drugs for this non-fatal complaint ? St. Andrew’s Hospital, Billericay, Essex.
IAN G. WICKES.
FAULTY TRACHEOSTOMY TUBE
SIR,-The accompanying photograph illustrates an extremely serious fault which developed in a recently
marketed plastic tracheostomy tube.1 The Nosworthy fitting has become partially detached from the tube. The manufacturers are investigating this matter. National Heart Hospital, London, W.1.
ALAN GILSTON.
HISTAMINE-INFUSION TEST
Mr. Laurie and his colleagues (Aug. 8) much. The inherently superior accuracy of protest intravenous infusions for administering histamine to stimulate gastric secretion has never been doubted; nevertheless this careful formal proof is welcome.
SIR,-Perhaps too
The histamine-infusion test does produce significantly more acid than the augmented histamine test. This would be a major advantage only if it improved the diagnostic discrimination between duodenal-ulcer and non-ulcer subjects. However, it seems unlikely that any modification of methods of measuring " maximum acid output " will much improve its diagnostic discrimination 2-about half the patients with duodenal ulcer secreting more than the upper limit of normal and about half normal subjects secreting less than the least value for a duodenal-ulcer patient2 3-since this functional discrimination merely mirrors the pathological difference in numbers of parietal cells in the stomach in duodenal-ulcer patients and normal subjects.4 The claim that " there is no need for radiological control of the position of the gastric tube " is surely retrogressive. Anacidity or achylia have not been demonstrated unless a tube tip is seen to lie in the body of the stomach and not, for instance, in the cardia, oesophagus, duodenum, or bronchus as may easily happen if the tube is blindly passed.5 6 Furthermore an intravenous infusion requires a constant-infusion pump and is surely less simple a procedure than a subcutaneous
injection. Incidentally,
those who possess neither a pH meter nor an automatic titrator can be reassured that titratable acidity can 1. See Whittard, B. R., Thomas, K. E. Lancet, 1964, i, 797. 2. Baron, J. H. Gut, 1963, 4, 243. 3. Grossman, M. I., Kirsner, J. B., Gillespie, I. E. Gastroenterology, 1963, 45, 14. 4. Cox, A. J. Arch. Path. 1952, 54, 407. 5. Callender, S. T., Retief, F. P., Witts, L. J. Gut, 1960, 1, 326. 6.
Baron, J. H. ibid. 1963, 4, 136.
be accurately measured by titrating colorimetrically micro-burette and the indicator phenol-red.7 Institute of Clinical Research, Middlesex Hospital Medical School, London, W.1.
using
a
J. H. BARON.
CANCER RESEARCH
SIR,-Following the further correspondence and the editorial comment on this subject, provoked by my earlier letter of Aug. 1, I wish to add just three points which will I believe adequately cover the most important features of the discussion thus far.
Firstly, I must reject any imputation that the financial arrangement existing between myself and the R.M.E.A. may result in the production of " biased conclusions ". Secondly, I believe there to be some confusion about the current usage and hazards of aldol-alphanaphthylamine. I am aware of the German source of this material and accept the statements that small quantities have been offered for sale and bought in this country. What may not be generally appreciated is that the manufacturers state clearly that they are described by Scott and Williams,8 as using a solvent process being capable of " reducing the unreacted amine to negligible quantities ". I have before me a categorical assurance from the manufacturers, dated May 22, 1964, that " adol-alphanaphthylamine powder... no longer contains the betanaphthylamine content of the basic alphanaphthylamine, whilst in the case of the resin this contamination is eliminated due to the difference in manufacturing methods ". They further state that a search of all relevant literature has shown no results of experiments on animals to suggest that aldol-alphanaphthylamine has any carcinogenic action and report that since the manufacture of
aldol-alphanaphthylamine was started at their factory in 1928 they have no record of any case of bladder cancer arising amongst any of their employees. My third and final point refers to the suggestions that an independent and impartial investigation of the rubber industry position should now be carried out. Contrary to what has been suggested, considerations of possible litigation and the economic consequences of divulging trade secrets do not weigh so heavily as to blind the majority of employers to their moral obligations. Deeply interested as I am personally in the problem of occupational bladder tumours, I would welcome all such assistance and advice as may be available from a team of independent and expert investigators looking further into this matter. Furthermore, I am now authorised by the chairman of the R.M.E.A. to state that the Association will willingly give its full cooperation and assistance to such an investigation and particularly welcomes the suggestion of Dr. Case (Aug. 8) that this might be appropriately carried out by the Statistical Research Unit of the Medical Research Council. I have accordingly now made an approach to the Medical Research Council to inquire whether
their Statistical Research Unit would be
prepared
to
undertake this task. R.M.E.A. Health Research 134, Edmund Street,
Birmingham,
3.
Unit,
GUY PARKES.
HYDROCEPHALUS ASSOCIATION
SIR,-For some time it has been apparent that an Association for parents of children with hydrocephalus or spina bifida is badly wanted. It is estimated that something like 3000 children a year are affected by these disorders. In the recent past very little could be done for them, and hence the majority (at least with spina bifida) did not survive long. These days, however, in some centres very active treatment is carried out, and in some larger units as many as 60-70% of all children with spina bifida survive for a long timesometimes up to school age. Their disabilities are neurological renal, orthopxdic, and educational. Fortunately, with modern treatment of hydrocephalus, something like two-thirds of all 7. Hollander, F. J. biol. Chem. 1931, 91, 481. 8. Scott, T. S., Williams, M. H. C. Brit. J. industr. Med. 1957, 14, 150.
grams
and it is reasonable to suppose that the same mechanisms are at work when these things occur in patients with oedema due to
pulmonary damage. Cardiovascular Findings The changing of the pulse with the phases of respiration and the improvement of blood-pressure wheni.p.p.R. was established were both probably related to the intrathoracic pressures, and similar changes may be seen in other circumstances. A high negative intrathoracic pressure will sometimes impede cardiac emptying during systole, and high positive pressures may enhance systolic emptying. Intra-arterial blood-pressure recording during positive-negative pressure ventilation shows swings of systolic pressure of up to 15 mm. Hg with the respiratory cycle., Rosen and Hillard have reported the deleterious effect of high intratracheal suction pressures on cardiac output.5 Patients with very laboured breathing may produce high negative intrathoracic pressures during inspiration. Tracheobronchitis Dr. Hunter also mentions the possibility that a " fibrinous tracheobronchitis " may have been in part responsible for these patients’ disabilities. While the damaged periphery of the lung may well be choked by a fibrinous exudate, we have experienced no difficulty in removing secretions by simple suction from the trachea and main bronchi whether these secretions were infected or sterile on culture. If secretions tend to block the main airways, I can only believe that this is due to inadequate humidification rather than to some cause peculiar to this type of patient. Newcastle General Hospital, Newcastle upon Tyne, 4.
M. MARSHALL.
CHEMICAL PATHOLOGIST SIR,-Your review of Techniques in Chemical Pathology (Aug. 1) refers to the author, Mr. G. A. Cheyne, F.I.M.L.T., as a chemical pathologist. To forestall perpetuation of an error which has caused controversy in the past, I write to point out that, in reference of medicine, the term " pathologist " should be applied only to the possessor of
medical
qualification. Mr. Cheyne is a highly skilled practitioner of a service ancillary to medicine but not of medicine. He should be described as a hospital " or a
"
"
clinical " biochemist but
chemical pathologist. S. C. DYKE
not as a
Chairman, Wolverhampton, Staffordshire.
Ethics and Professional Affairs Committee, Association of Clinical Pathologists.
PHENOTHIAZINE DYSKINESIA AFTER
LEUCOTOMY annotation SIR,-In your (Aug. 1) you suggest that the effect of neuronal degeneration, secondary to leucotomy, might so synergise with the chemical action of to engender chorea. No such as phenothiazines " chemical and structural synergism " is required for the development of chorea by chlordiazepoxide. A patient who came under my notice, and whose case was briefly recorded by Macleodmanifested typical chorea affecting predominantly the face, tongue and hands " after "
a
short
of treatment movements
course
involuntary treatment
was
with chlordiazepoxide. These disappeared some months after this
discontinued.
It is
perhaps significant that, of a large number of tried for the control of Huntington’s chorea, drugs Warwick and Barrowsfound chlordiazepoxide by far the most effective. SIMON BEBRMAN. BEHRMAN. London, W.1. 5. 6. 7.
Rosen, M., Hillard, E. K. Curr. Res. Anesth. Analg. 1962, 41, 50. Macleod, D. M. Lancet, 1964, i, 388. Warwick, L. H., Barrows, H. S. Bull. Los Angeles neurol. Soc. 1964, 20, 17.
HÆMODILUTION ANÆMIA ASSOCIATED WITH SIMPLE SPLENIC HYPERPLASIA SIR,-Dr. Weinstein suggests in his interesting paper (Aug. 1) that alteration in plasma oncotic pressure could account
for increased plasma-volume.
4 of his 5 patients had abnormalities in the pattern of their plasma-protein. Hsmodilution of this type can also be developed in hyperimmunised rabbits with very high serumgammaglobulin levels,l-3 and McCance and Widdowson4 have shown that newborn piglets receiving colostrum exhibit an increase in serum-gammaglobulin and plasma-volume. It would be interesting to know the plasma-cell concen-
tration in bone-marrow and spleen and the serum-electrophoresis in Dr. Weinstein’s cases 1-4. Medical Department B,
Bispebjerg Hospital, Copenhagen.
M.
BJØRNEBOE.
TREATMENT OF ENURESIS
SIR,-I, too, was horrified at the treatments for enuresis mentioned in your leading article, and in the subsequent letters. Dr. Murray (Aug. 15) says that enuretic children " pass abnormally large quantities of urine during the night and on rising ". Some time ago I measured the urine passed by some enuretic teenagers, and found that the amount of urine passed first thing in the morning averaged 5 oz. in 226 measurings. In one boy, it was never more than 3 oz. whether his bed was wet or dry. It takes very little fluid to soak a bed, as anyone will know if they have ever upset a cup of tea. During an investigation of the intake/output of pregnant women5 it was found that those women who had to pass urine several times in the night, passed (in a 24-hour period) less than those who had no nocturia. Reducing the fluid intake helped neither the pregnant women with nocturia nor the teenagers with enuresis. I agree with Dr. Gutierrez that the cause of enuresis has something to do with the nervous system, although psychotherapy has not improved any of my teenagers. The trouble seems to be physiological rather than psychological. In the above-mentioned investigation, it was found that nocturia could be cured in pregnant women. The same treatment was given to teenager enuretics, and the number of wet beds per week was reduced, but so far a complete cure has not been obtained. The teenagers also became conscious of wanting to pass water in the night, and, for the first time in their lives, they woke up and passed water. Strangely enough, their beds were dry on the nights that they did not wake up and pass water. Work on the physiology of nerves might possibly lead to a better understanding of enuresis. The condition may also have something to do with growth, or the growth hormone, as spontaneous cure of nocturia in women usually occurs after the birth of the baby; and spontaneous cure of enuresis in children usually occurs during periods of little growth or at the end of adolescence when growth has ceased. Derby.
MARGARET ROBINSON.
SIR,-Ifail to see why Sir Francis Walshe should have been so depressed by your leading article of June 27; for it described a method which brings complete, or almost complete, relief to about 75% of persistent enuretics. In his bookhe refers to the " frequent failure of routine lines of treatment ... now available "; but, now that he is aware of the success of the buzzer, one would have expected him to be as delighted as are the many patients who have been cured by it. ...
Bjørneboe, M., Schwartz, M. J. exp. Med. 1959, 110, 259. Bjørneboe, M., Jarnum, S. ibid. 1961, 113, 1005. Rotschild, M. A., Oratz, M., Franklin, E. E., Schreiber, S. S. J. clin. Invest. 1962, 41, 1564. 4. McCance, R. A., Widdowson, E. M. J. Physiol. 1959, 145, 547. 5. Robinson, M. Med. Offr, 1964, 111, 75. 6. Diseases of the Nervous System 5th ed. (1947), p. 299; 9th ed. (1958), p. 328.
1. 2. 3.
414 Sir Francis goes so far as to describe an apparatus being similar to a front-door bell as a " barbarous contraption "; yet he was quite prepared to recommend strychnine and belladonna for this complaint in the earlier editions of his book, though (significantly) these have been changed for less dangerous drugs in the latest edition. Can anyone explain why some doctors react so violently and irrationally against the buzzer, yet appear to have no qualms in recommending the use of potentially lethal drugs for this non-fatal complaint ? St. Andrew’s Hospital, Billericay, Essex.
IAN G. WICKES.
FAULTY TRACHEOSTOMY TUBE
SIR,-The accompanying photograph illustrates an extremely serious fault which developed in a recently
marketed plastic tracheostomy tube.1 The Nosworthy fitting has become partially detached from the tube. The manufacturers are investigating this matter. National Heart Hospital, London, W.1.
ALAN GILSTON.
HISTAMINE-INFUSION TEST
Mr. Laurie and his colleagues (Aug. 8) much. The inherently superior accuracy of protest intravenous infusions for administering histamine to stimulate gastric secretion has never been doubted; nevertheless this careful formal proof is welcome.
SIR,-Perhaps too
The histamine-infusion test does produce significantly more acid than the augmented histamine test. This would be a major advantage only if it improved the diagnostic discrimination between duodenal-ulcer and non-ulcer subjects. However, it seems unlikely that any modification of methods of measuring " maximum acid output " will much improve its diagnostic discrimination 2-about half the patients with duodenal ulcer secreting more than the upper limit of normal and about half normal subjects secreting less than the least value for a duodenal-ulcer patient2 3-since this functional discrimination merely mirrors the pathological difference in numbers of parietal cells in the stomach in duodenal-ulcer patients and normal subjects.4 The claim that " there is no need for radiological control of the position of the gastric tube " is surely retrogressive. Anacidity or achylia have not been demonstrated unless a tube tip is seen to lie in the body of the stomach and not, for instance, in the cardia, oesophagus, duodenum, or bronchus as may easily happen if the tube is blindly passed.5 6 Furthermore an intravenous infusion requires a constant-infusion pump and is surely less simple a procedure than a subcutaneous
injection. Incidentally,
those who possess neither a pH meter nor an automatic titrator can be reassured that titratable acidity can 1. See Whittard, B. R., Thomas, K. E. Lancet, 1964, i, 797. 2. Baron, J. H. Gut, 1963, 4, 243. 3. Grossman, M. I., Kirsner, J. B., Gillespie, I. E. Gastroenterology, 1963, 45, 14. 4. Cox, A. J. Arch. Path. 1952, 54, 407. 5. Callender, S. T., Retief, F. P., Witts, L. J. Gut, 1960, 1, 326. 6.
Baron, J. H. ibid. 1963, 4, 136.
be accurately measured by titrating colorimetrically micro-burette and the indicator phenol-red.7 Institute of Clinical Research, Middlesex Hospital Medical School, London, W.1.
using
a
J. H. BARON.
CANCER RESEARCH
SIR,-Following the further correspondence and the editorial comment on this subject, provoked by my earlier letter of Aug. 1, I wish to add just three points which will I believe adequately cover the most important features of the discussion thus far.
Firstly, I must reject any imputation that the financial arrangement existing between myself and the R.M.E.A. may result in the production of " biased conclusions ". Secondly, I believe there to be some confusion about the current usage and hazards of aldol-alphanaphthylamine. I am aware of the German source of this material and accept the statements that small quantities have been offered for sale and bought in this country. What may not be generally appreciated is that the manufacturers state clearly that they are described by Scott and Williams,8 as using a solvent process being capable of " reducing the unreacted amine to negligible quantities ". I have before me a categorical assurance from the manufacturers, dated May 22, 1964, that " adol-alphanaphthylamine powder... no longer contains the betanaphthylamine content of the basic alphanaphthylamine, whilst in the case of the resin this contamination is eliminated due to the difference in manufacturing methods ". They further state that a search of all relevant literature has shown no results of experiments on animals to suggest that aldol-alphanaphthylamine has any carcinogenic action and report that since the manufacture of
aldol-alphanaphthylamine was started at their factory in 1928 they have no record of any case of bladder cancer arising amongst any of their employees. My third and final point refers to the suggestions that an independent and impartial investigation of the rubber industry position should now be carried out. Contrary to what has been suggested, considerations of possible litigation and the economic consequences of divulging trade secrets do not weigh so heavily as to blind the majority of employers to their moral obligations. Deeply interested as I am personally in the problem of occupational bladder tumours, I would welcome all such assistance and advice as may be available from a team of independent and expert investigators looking further into this matter. Furthermore, I am now authorised by the chairman of the R.M.E.A. to state that the Association will willingly give its full cooperation and assistance to such an investigation and particularly welcomes the suggestion of Dr. Case (Aug. 8) that this might be appropriately carried out by the Statistical Research Unit of the Medical Research Council. I have accordingly now made an approach to the Medical Research Council to inquire whether
their Statistical Research Unit would be
prepared
to
undertake this task. R.M.E.A. Health Research 134, Edmund Street,
Birmingham,
3.
Unit,
GUY PARKES.
HYDROCEPHALUS ASSOCIATION
SIR,-For some time it has been apparent that an Association for parents of children with hydrocephalus or spina bifida is badly wanted. It is estimated that something like 3000 children a year are affected by these disorders. In the recent past very little could be done for them, and hence the majority (at least with spina bifida) did not survive long. These days, however, in some centres very active treatment is carried out, and in some larger units as many as 60-70% of all children with spina bifida survive for a long timesometimes up to school age. Their disabilities are neurological renal, orthopxdic, and educational. Fortunately, with modern treatment of hydrocephalus, something like two-thirds of all 7. Hollander, F. J. biol. Chem. 1931, 91, 481. 8. Scott, T. S., Williams, M. H. C. Brit. J. industr. Med. 1957, 14, 150.