- Email: [email protected]
ACUTE SALICYLATE POISONING
1312 enteritis
that
unit, severely
so
for the past 4 years;
we
have found
seriously affected seem to respond just as adequately without, as with, antibiotic treatment when accepted measures directed at restoring and maintaining electrolyte and fluid balance are efficiently applied, coupled with skilled nursing. It is significant that of the 58 seriously ill babies admitted to our gastroenteritis unit in the past 4 years, only 7 were found to be excreting E. coli (bowel pathogens were isolated from 2 others; one had Shigella infection, the other Salmonella). Furthermore, none of the 7 fatal cases occurring in this period were excreting E. coli. even
those
outbreak of E. coli gastroa nursery in a maternity department, one has no alternative but to administer, without delay, an appropriate antibiotic, treating not only those with symptoms but all immediate contacts. Royal Alexandra Hospital for Sick Children, TREVOR P. MANN. Brighton 1.
Needless enteritis in
to
say, faced with
an
a
pxdiatric ward
or
ACUTE SALICYLATE POISONING SiR,—Your leader (May 24, p. 1038) states that " it is pertinent to reconsider the aim of treatment in acute salicylate intoxication " and the ensuing discussion of the accompanying acid-base disturbance suggests that you believe that therapy should be directed at this feature, rather than at the elimination of salicylate. Symptomatic treatment of any condition is fundamentally unacceptable, and in salicylate poisoning in particular it is unnecessary. Surely it is more logical to treat the already complex metabolic disturbance by removing the cause-i.e., salicylate-than to complicate the situation further by attempting the manoeuvres suggested. There is no evidence that the acid-base disturbance which is usually present in adults is in any way harmful or requires treatment. It is more important to be aware of the small minority who may be acidxmic.1 We fail to see how the aim of treatment in salicylate poisoning can be other than to increase the elimination of the poison, and we reiterate our claim that our regimen2 achieves this at a
satisfactory SIR,-Like Dr. Valman and Dr. Wilmers we are engaged in the care of infants with acute gastroenteritis; but unlike them we do not routinely use antibiotics. We agree about the fundamental importance of careful intravenous infusion in these cases. At our hospital patients with the discharge diagnosis of gastroenteritis total about 300 each year, and the vast majority are under three years old. Excluded from this total are patients with salmonella and shigella infections. The mortality is under 1%. It is not clear from the paper by Dr. Valman and Dr. Wilmers whether neomycin was prescribed routinely to the 6 infants who developed severe gastroenteritis presumably as a result of cross-infection. (They say that neomycin is given routinely to all patients except those on intravenous fluids.) If in fact neomycin was prescribed, the diarrhoea and the multiple resistance of the pathogenic Escherichia coli to this antibiotic were, possibly, the result of its administration. Further, Dr. Valman and Dr. Wilmers do not indicate whether antibiotics are prescribed to all infants with diarrhoea, if this is their policy a high proportion of their patients from whom a gastroenteritic pathogen is not isolated must receive drugs. Nor do they state what proportion of the 224 infants admitted to their unit in 1968 with gastroenteritis had enteropathogenic E. coli infections. The evidence presented by these workers surely contradicts their claim that administration of an effective antibiotic to all infants below the age of two years prevents cross-infection and recurrence of diarrhoea, assuming that those infants who were cross-infected received neomycin. Our view is that, by using antibiotics, resistant strains are encouraged to flourish so that when cross-infection does occur it is caused by organisms resistant to the drug routinely prescribed. Administration of antibiotics may be conducive to cross-infection. We have come to believe that intestinal infections due to salmonella: (excluding typhoid and bloodstream infections), shigellae, and enteropathogenic strains of E. coli behave in a similar way in relation to antibiotic therapy. That is to say, acute symptoms are not relieved, and clearance of the organism from the faeces is not expedited by antibiotics. In relation to salmonella infections we say this with some confidence, for there is good published evidence supporting our contention. We ourselves have published data1 showing similar results in a small series of shigella infections. We have not yet published a controlled trial of enteropathogenic E. coli infections. We agree with Ramsay2 that " Except in the case of invasive salmonella infections and the Flexner form of dysentery antibiotics have no place in treatment ". R. T. D. EMOND Coppetts Wood Hospital, Muswell Hill, London N.10. 1. 2.
J. A. GRAY HILLAS SMITH
important dehydration, produces
occasions. Regional Poisoning Treatment Centre, Royal Infirmary, Edinburgh EH3 9YW.
HENRY MATTHEW A. T. PROUDFOOT S. S. BROWN A. A. H. LAWSON.
*** We regret that Dr. Matthew and his colleagues found so much that was unacceptable in our leader. We had intended only to suggest that the continuing mortality in salicylate intoxication, and indeed the cause of death, remain unexplained and that it seems likely that the answers may be found in the acid-base disturbance. We doubt whether correction of acid-base and electrolyte upsets should be regarded as " symptomatic treatment", but we would, of course, concede that efforts to remove any poison are worth while. Certainly, intensive biochemical monitoring is not possible everywhere, but, so long as controversy persists about the best form of treatment, there is much to be said for intensive monitoring when the resources are available. Finally, 1. 2.
S. E. J. YOUNG.
Smith, H., Young, S. E. J. Br. med. J. 1966, i, 481. Ramsay, A. M. ibid. 1968, ii, 347.
rate, corrects
minimal exacerbation of the acid-base disturbance, and avoids dangerous hypokalaemia. Since the paper was submitted a further 52 patients have been uneventfully treated by this means without biochemical monitoring. It would be foolish to suggest that any regimen used blindly is completely without hazard, but no more so than to believe that most hospitals can conjure up at short notice " intensive biochemical monitoring ", which your leader states is necessary. Such monitoring would be mandatory if one attempted to correct the acid-base disturbance using the measures suggested-i.e., depressing respiration with barbiturates or adding carbon dioxide to the inspired air. We strongly suggest that you venture outside your ivory tower. In general the leader is vague, unhelpful, and inaccurate. The issue is confused by meaningless comparison with barbiturate poisoning. Whereas salicylic acid is a single substance the barbiturates are a group whose members are metabolised and excreted in different ways. It is highly misleading, therefore, to state that " forced diuresis and haemodialysis remove salicylate at least as effectively as they do the barbi" for there is good evidence 34 that these techniques turates are only of real value in a small minority of cases of acute barbiturate poisoning. Furthermore the 1 % mortality in 776 cases of barbiturate poisoning in this centre, cited 5 as an example of what can be achieved by using forced diuresis or haemodialysis, was, in fact, obtained without recourse to hsemodialysis, and forced diuresis was used on only four
3. 4. 5.
Proudfoot, A. T., Brown, S. S. Br. med. J., May 31, 1969, ii, p. 547. Lawson, A. A. H., Proudfoot, A. T., Brown, S. S., Macdonald, R. H., Fraser, A. G., Cameron, J. C., Matthew, H. Q. Jl Med. 1969, 38, 31. Bloomer, H. A. Lancet, 1967, ii, 986. Mawer, G. W., Lee, H. A. A. Br. med. J. 1968, ii, 790. Matthew, H., Lawson, A. A. H. Q. Jl Med. 1966, 35, 539.
1313 we were making no claims for the efficacy of forced diuresis and haemodialysis in the removal of any specific type of barbiturate: we were simply trying to indicate that, although -these techniques are known to remove large amounts of salicylates, the mortality-rate in salicylate intoxication remains higher than that in barbiturate poisoning.-ED. L.
BLOOD GASES AND LUNG FUNCTION SIR,-Dr. Palmer and Dr. Diament are to be commended for providing your readers with further data on interrelationships between the physiological changes in chronic obstructive pulmonary disease (May 31, p. 1073). Many, however, may take exception to their closing claim to be able to predict probable values for arterial oxygen tension (Pao2) and carbondioxide tension (Paco2) from a knowledge of the F.E.V.I. They show significant correlation coefficients, but at a lower value than is usually acceptable for prediction purposes. This is borne out by their standard errors of approximately 11 mm. Hg for predicted Pao2 and P aC02’ Thus, in patients categorised by the authors as severe (F.E.V’l less than 40%), the mean F.E.V’l was 0-63 litres (33%). At this level, the mean Pa02 was 68 mm. Hg and the PaC02, 61 mm. Hg. Even at this optimum point for prediction, however, the 95% range for Pa02 would lie between 44 and 92 mm. Hg and for Paco2 between 38 and 84 mm. Hg. Since these ranges include normal and distinctly abnormal values, I suggest that the authors’ claim is unwarranted and that serious errors of judgment could arise from the use of their equations for prediction purposes. A more philosophical comment might be made on the use of oxygen-tension values in a linear regression, when the former include extremely low values. Since pulmonary-venousadmixture effect is produced by a mixing of saturated and unsaturated blood, a linear relationship might exist between the degree of lung change and the arterial oxygen content. The latter is related in very non-linear fashion to oxygen tension, and therefore the slope of linear regressions predicting oxygen tension may be biased according to the level of the data for oxygen tension from which the equation is derived. A correlation which was not reported in the paper is that between arterial-oxygen tension and the single-breath carbonmonoxide-transfer factor. Many hospitals which have no facilities for measuring diffusing capacity are able to measure arterial-oxygen tensions. It would be interesting to know with what accuracy the diffusing capacity could, in fact, be predicted from a knowledge of the arterial-oxygen tension or the alveolar-arterial oxygen gradient. Department of Anesthesia, Veterans Administration Hospital, H. BARRIE FAIRLEY. San Francisco, California 94121.
CONDITIONS IN PSYCHIATRIC HOSPITALS SIR,-Dr. Freeman (June 7, p. 1151) rightly emphasises the need to plan services without depending on large additional financial resources. There are, however, several reasons for not using " decrepit old houses " as hostels: standards must not be set too low, and I think most local authorities would hesitate to spend public money on what can prove to be an expensive venture when it comes to maintenance. Ordinary houses in reasonable condition are a different matter, and the Phoenix Group Homes Scheme1 is a striking example of what a voluntary organisation can do, especially when the local health authority cooperates closely. It is encouraging that the scheme has gained considerable momentum since its inception. The abolition of the large institutions advocated by Dr. Freeman and many others, seems to be, at least in the field of subnormality, an ideal incompatible with financial stringency. I have yet to meet a colleague (nursing or medical) working in subnormality who would not dearly love to have small units of 24 or less patients, where the work would be more satisfying 1. See
Lancet, 1966, i, 1276.
and the patients would do better. One hopes that small experimental units will be promoted wherever possible, but most of us, I believe, must accept the challenge of providing the best possible care in the existing large hospitals for very many years to come. The policies, already in practice in many subnormality hospitals, of developing and reorientating the service from within the hospital must therefore be supported. The service must not be allowed to deteriorate by default. It would be an enormous improvement if large wards were broken down into small units aiming, at least in the sphere of subnormality, at village-type communities-a policy which is not so idealistic as to be unrealistic. Policies which concentrate only on alternatives to hospital care are bound to be demoralising-and possibly dangerously so-to those, especially nursing staff, who continue to carry the responsibility of caring for such large numbers of patients. At least in subnormality, Mr. Crossman’s decision to apply pressure to increase expenditure on hospitals is more than justified under these circumstances. South Ockenden Hospital, Essex.
M. E. YORK-MOORE.
DISCRIMINANTS AND BREAST CANCER SIR,-Dr. Bulbrook and Mr. Hayward refer in their letter (June 7, p. 1161) to our findingl that the occurrence of a negative discriminant in breast cancer (our " alternative discriminant "2) was associated with the age of the patient and the stage of the disease. In our menopausal group (aged 50 years or more), negative discriminants occurred with equal frequency in the normal women and in those with the disease, except for a marginal excess in women presenting in the advanced stages. In the premenopausal group, none of our normal subjects had a negative discriminant; but the incidence of negative discriminants, at presentation with the disease, increased with the severity of the disease as judged by clinical and histological
staging. Nabarro3 suggested that negative discriminants were to be expected in women with advanced breast cancer, since the associated debility would cause a rise in corticosteroid excretion and a fall in astiocholanolone excretion. In our patients, however, the majority of negative discriminants were due to falls in androgen excretion (11-D.K.s.) rather than to rises in corticosteroid excretion (17-0He.s.).l Furthermore, in our normal series we have noted that 11-D.K.s. excretion falls rapidly around 50 years of age. It has recently been reported that postmenopausal women with endometrial cancer also have negative discriminants based on xtiocholanolone and 17-OHc.s. excretion.4 We are currently examining a number of factors which might affect our alternative discriminant, and are confining our studies to women aged 49 years and under. We have found that surgical " stress " itself does not alter the discriminant. Advanced non-mammary cancer is frequently associated with a negative discriminant, but early non-mammary cancer is not. Liver disease with jaundice, whether metastatic, obstructive, or hepatotoxic, usually is associated with a negative discriminant. Here again, it is the decreased androgens that matter, rather than any rise in corticosteroids. Bulbrook et al. have shown that a good response to endocrine-organ ablation in cases of advanced breast cancer is more likely to be associated with a positive discriminant than with a negative discriminant. Our preliminary findings with the non-mammary factors mentioned above, lead us to consider the possibility that a positive discriminant indicates that, even though the patient is in the advanced stages of the disease, the 1. 2. 3. 4. 5.
Miller, H., Durant, J. A. Clin. Biochem. 1968, 1, 287. Miller, H., Durant, J. A., Jacobs, A. G., Allison, J. F. Br. med. J. 1967, i, 147. Nabarro, J. D. N. Lancet, 1960, i, 1293. De Waard, F., Thyssen, J. H. H., Veeman, W., Sander, P. C. Cancer, N.Y. 1968, 22, 988. Bulbrook, R. D., Greenwood, F. C., Hayward, J. L. Lancet, 1910, i, 1154.
that
unit, severely
so
for the past 4 years;
we
have found
seriously affected seem to respond just as adequately without, as with, antibiotic treatment when accepted measures directed at restoring and maintaining electrolyte and fluid balance are efficiently applied, coupled with skilled nursing. It is significant that of the 58 seriously ill babies admitted to our gastroenteritis unit in the past 4 years, only 7 were found to be excreting E. coli (bowel pathogens were isolated from 2 others; one had Shigella infection, the other Salmonella). Furthermore, none of the 7 fatal cases occurring in this period were excreting E. coli. even
those
outbreak of E. coli gastroa nursery in a maternity department, one has no alternative but to administer, without delay, an appropriate antibiotic, treating not only those with symptoms but all immediate contacts. Royal Alexandra Hospital for Sick Children, TREVOR P. MANN. Brighton 1.
Needless enteritis in
to
say, faced with
an
a
pxdiatric ward
or
ACUTE SALICYLATE POISONING SiR,—Your leader (May 24, p. 1038) states that " it is pertinent to reconsider the aim of treatment in acute salicylate intoxication " and the ensuing discussion of the accompanying acid-base disturbance suggests that you believe that therapy should be directed at this feature, rather than at the elimination of salicylate. Symptomatic treatment of any condition is fundamentally unacceptable, and in salicylate poisoning in particular it is unnecessary. Surely it is more logical to treat the already complex metabolic disturbance by removing the cause-i.e., salicylate-than to complicate the situation further by attempting the manoeuvres suggested. There is no evidence that the acid-base disturbance which is usually present in adults is in any way harmful or requires treatment. It is more important to be aware of the small minority who may be acidxmic.1 We fail to see how the aim of treatment in salicylate poisoning can be other than to increase the elimination of the poison, and we reiterate our claim that our regimen2 achieves this at a
satisfactory SIR,-Like Dr. Valman and Dr. Wilmers we are engaged in the care of infants with acute gastroenteritis; but unlike them we do not routinely use antibiotics. We agree about the fundamental importance of careful intravenous infusion in these cases. At our hospital patients with the discharge diagnosis of gastroenteritis total about 300 each year, and the vast majority are under three years old. Excluded from this total are patients with salmonella and shigella infections. The mortality is under 1%. It is not clear from the paper by Dr. Valman and Dr. Wilmers whether neomycin was prescribed routinely to the 6 infants who developed severe gastroenteritis presumably as a result of cross-infection. (They say that neomycin is given routinely to all patients except those on intravenous fluids.) If in fact neomycin was prescribed, the diarrhoea and the multiple resistance of the pathogenic Escherichia coli to this antibiotic were, possibly, the result of its administration. Further, Dr. Valman and Dr. Wilmers do not indicate whether antibiotics are prescribed to all infants with diarrhoea, if this is their policy a high proportion of their patients from whom a gastroenteritic pathogen is not isolated must receive drugs. Nor do they state what proportion of the 224 infants admitted to their unit in 1968 with gastroenteritis had enteropathogenic E. coli infections. The evidence presented by these workers surely contradicts their claim that administration of an effective antibiotic to all infants below the age of two years prevents cross-infection and recurrence of diarrhoea, assuming that those infants who were cross-infected received neomycin. Our view is that, by using antibiotics, resistant strains are encouraged to flourish so that when cross-infection does occur it is caused by organisms resistant to the drug routinely prescribed. Administration of antibiotics may be conducive to cross-infection. We have come to believe that intestinal infections due to salmonella: (excluding typhoid and bloodstream infections), shigellae, and enteropathogenic strains of E. coli behave in a similar way in relation to antibiotic therapy. That is to say, acute symptoms are not relieved, and clearance of the organism from the faeces is not expedited by antibiotics. In relation to salmonella infections we say this with some confidence, for there is good published evidence supporting our contention. We ourselves have published data1 showing similar results in a small series of shigella infections. We have not yet published a controlled trial of enteropathogenic E. coli infections. We agree with Ramsay2 that " Except in the case of invasive salmonella infections and the Flexner form of dysentery antibiotics have no place in treatment ". R. T. D. EMOND Coppetts Wood Hospital, Muswell Hill, London N.10. 1. 2.
J. A. GRAY HILLAS SMITH
important dehydration, produces
occasions. Regional Poisoning Treatment Centre, Royal Infirmary, Edinburgh EH3 9YW.
HENRY MATTHEW A. T. PROUDFOOT S. S. BROWN A. A. H. LAWSON.
*** We regret that Dr. Matthew and his colleagues found so much that was unacceptable in our leader. We had intended only to suggest that the continuing mortality in salicylate intoxication, and indeed the cause of death, remain unexplained and that it seems likely that the answers may be found in the acid-base disturbance. We doubt whether correction of acid-base and electrolyte upsets should be regarded as " symptomatic treatment", but we would, of course, concede that efforts to remove any poison are worth while. Certainly, intensive biochemical monitoring is not possible everywhere, but, so long as controversy persists about the best form of treatment, there is much to be said for intensive monitoring when the resources are available. Finally, 1. 2.
S. E. J. YOUNG.
Smith, H., Young, S. E. J. Br. med. J. 1966, i, 481. Ramsay, A. M. ibid. 1968, ii, 347.
rate, corrects
minimal exacerbation of the acid-base disturbance, and avoids dangerous hypokalaemia. Since the paper was submitted a further 52 patients have been uneventfully treated by this means without biochemical monitoring. It would be foolish to suggest that any regimen used blindly is completely without hazard, but no more so than to believe that most hospitals can conjure up at short notice " intensive biochemical monitoring ", which your leader states is necessary. Such monitoring would be mandatory if one attempted to correct the acid-base disturbance using the measures suggested-i.e., depressing respiration with barbiturates or adding carbon dioxide to the inspired air. We strongly suggest that you venture outside your ivory tower. In general the leader is vague, unhelpful, and inaccurate. The issue is confused by meaningless comparison with barbiturate poisoning. Whereas salicylic acid is a single substance the barbiturates are a group whose members are metabolised and excreted in different ways. It is highly misleading, therefore, to state that " forced diuresis and haemodialysis remove salicylate at least as effectively as they do the barbi" for there is good evidence 34 that these techniques turates are only of real value in a small minority of cases of acute barbiturate poisoning. Furthermore the 1 % mortality in 776 cases of barbiturate poisoning in this centre, cited 5 as an example of what can be achieved by using forced diuresis or haemodialysis, was, in fact, obtained without recourse to hsemodialysis, and forced diuresis was used on only four
3. 4. 5.
Proudfoot, A. T., Brown, S. S. Br. med. J., May 31, 1969, ii, p. 547. Lawson, A. A. H., Proudfoot, A. T., Brown, S. S., Macdonald, R. H., Fraser, A. G., Cameron, J. C., Matthew, H. Q. Jl Med. 1969, 38, 31. Bloomer, H. A. Lancet, 1967, ii, 986. Mawer, G. W., Lee, H. A. A. Br. med. J. 1968, ii, 790. Matthew, H., Lawson, A. A. H. Q. Jl Med. 1966, 35, 539.
1313 we were making no claims for the efficacy of forced diuresis and haemodialysis in the removal of any specific type of barbiturate: we were simply trying to indicate that, although -these techniques are known to remove large amounts of salicylates, the mortality-rate in salicylate intoxication remains higher than that in barbiturate poisoning.-ED. L.
BLOOD GASES AND LUNG FUNCTION SIR,-Dr. Palmer and Dr. Diament are to be commended for providing your readers with further data on interrelationships between the physiological changes in chronic obstructive pulmonary disease (May 31, p. 1073). Many, however, may take exception to their closing claim to be able to predict probable values for arterial oxygen tension (Pao2) and carbondioxide tension (Paco2) from a knowledge of the F.E.V.I. They show significant correlation coefficients, but at a lower value than is usually acceptable for prediction purposes. This is borne out by their standard errors of approximately 11 mm. Hg for predicted Pao2 and P aC02’ Thus, in patients categorised by the authors as severe (F.E.V’l less than 40%), the mean F.E.V’l was 0-63 litres (33%). At this level, the mean Pa02 was 68 mm. Hg and the PaC02, 61 mm. Hg. Even at this optimum point for prediction, however, the 95% range for Pa02 would lie between 44 and 92 mm. Hg and for Paco2 between 38 and 84 mm. Hg. Since these ranges include normal and distinctly abnormal values, I suggest that the authors’ claim is unwarranted and that serious errors of judgment could arise from the use of their equations for prediction purposes. A more philosophical comment might be made on the use of oxygen-tension values in a linear regression, when the former include extremely low values. Since pulmonary-venousadmixture effect is produced by a mixing of saturated and unsaturated blood, a linear relationship might exist between the degree of lung change and the arterial oxygen content. The latter is related in very non-linear fashion to oxygen tension, and therefore the slope of linear regressions predicting oxygen tension may be biased according to the level of the data for oxygen tension from which the equation is derived. A correlation which was not reported in the paper is that between arterial-oxygen tension and the single-breath carbonmonoxide-transfer factor. Many hospitals which have no facilities for measuring diffusing capacity are able to measure arterial-oxygen tensions. It would be interesting to know with what accuracy the diffusing capacity could, in fact, be predicted from a knowledge of the arterial-oxygen tension or the alveolar-arterial oxygen gradient. Department of Anesthesia, Veterans Administration Hospital, H. BARRIE FAIRLEY. San Francisco, California 94121.
CONDITIONS IN PSYCHIATRIC HOSPITALS SIR,-Dr. Freeman (June 7, p. 1151) rightly emphasises the need to plan services without depending on large additional financial resources. There are, however, several reasons for not using " decrepit old houses " as hostels: standards must not be set too low, and I think most local authorities would hesitate to spend public money on what can prove to be an expensive venture when it comes to maintenance. Ordinary houses in reasonable condition are a different matter, and the Phoenix Group Homes Scheme1 is a striking example of what a voluntary organisation can do, especially when the local health authority cooperates closely. It is encouraging that the scheme has gained considerable momentum since its inception. The abolition of the large institutions advocated by Dr. Freeman and many others, seems to be, at least in the field of subnormality, an ideal incompatible with financial stringency. I have yet to meet a colleague (nursing or medical) working in subnormality who would not dearly love to have small units of 24 or less patients, where the work would be more satisfying 1. See
Lancet, 1966, i, 1276.
and the patients would do better. One hopes that small experimental units will be promoted wherever possible, but most of us, I believe, must accept the challenge of providing the best possible care in the existing large hospitals for very many years to come. The policies, already in practice in many subnormality hospitals, of developing and reorientating the service from within the hospital must therefore be supported. The service must not be allowed to deteriorate by default. It would be an enormous improvement if large wards were broken down into small units aiming, at least in the sphere of subnormality, at village-type communities-a policy which is not so idealistic as to be unrealistic. Policies which concentrate only on alternatives to hospital care are bound to be demoralising-and possibly dangerously so-to those, especially nursing staff, who continue to carry the responsibility of caring for such large numbers of patients. At least in subnormality, Mr. Crossman’s decision to apply pressure to increase expenditure on hospitals is more than justified under these circumstances. South Ockenden Hospital, Essex.
M. E. YORK-MOORE.
DISCRIMINANTS AND BREAST CANCER SIR,-Dr. Bulbrook and Mr. Hayward refer in their letter (June 7, p. 1161) to our findingl that the occurrence of a negative discriminant in breast cancer (our " alternative discriminant "2) was associated with the age of the patient and the stage of the disease. In our menopausal group (aged 50 years or more), negative discriminants occurred with equal frequency in the normal women and in those with the disease, except for a marginal excess in women presenting in the advanced stages. In the premenopausal group, none of our normal subjects had a negative discriminant; but the incidence of negative discriminants, at presentation with the disease, increased with the severity of the disease as judged by clinical and histological
staging. Nabarro3 suggested that negative discriminants were to be expected in women with advanced breast cancer, since the associated debility would cause a rise in corticosteroid excretion and a fall in astiocholanolone excretion. In our patients, however, the majority of negative discriminants were due to falls in androgen excretion (11-D.K.s.) rather than to rises in corticosteroid excretion (17-0He.s.).l Furthermore, in our normal series we have noted that 11-D.K.s. excretion falls rapidly around 50 years of age. It has recently been reported that postmenopausal women with endometrial cancer also have negative discriminants based on xtiocholanolone and 17-OHc.s. excretion.4 We are currently examining a number of factors which might affect our alternative discriminant, and are confining our studies to women aged 49 years and under. We have found that surgical " stress " itself does not alter the discriminant. Advanced non-mammary cancer is frequently associated with a negative discriminant, but early non-mammary cancer is not. Liver disease with jaundice, whether metastatic, obstructive, or hepatotoxic, usually is associated with a negative discriminant. Here again, it is the decreased androgens that matter, rather than any rise in corticosteroids. Bulbrook et al. have shown that a good response to endocrine-organ ablation in cases of advanced breast cancer is more likely to be associated with a positive discriminant than with a negative discriminant. Our preliminary findings with the non-mammary factors mentioned above, lead us to consider the possibility that a positive discriminant indicates that, even though the patient is in the advanced stages of the disease, the 1. 2. 3. 4. 5.
Miller, H., Durant, J. A. Clin. Biochem. 1968, 1, 287. Miller, H., Durant, J. A., Jacobs, A. G., Allison, J. F. Br. med. J. 1967, i, 147. Nabarro, J. D. N. Lancet, 1960, i, 1293. De Waard, F., Thyssen, J. H. H., Veeman, W., Sander, P. C. Cancer, N.Y. 1968, 22, 988. Bulbrook, R. D., Greenwood, F. C., Hayward, J. L. Lancet, 1910, i, 1154.