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MUSCLE DISEASE IN CHRONIC ALCOHOLISM
1292
Letters
to
the Editor
EFFECT OF SILICONES ON THE ABSORPTION OF ANTICOAGULANT DRUGS SIR,-We wish to draw attention to the possible effect on the absorption of anticoagulant drugs of a substance allied to the silicones (methyl polysiloxane) which is present in certain proprietary brands of cooking oil as an additive. Its purpose is to give to potato chips an attractive crisp, dry appearance, for which it is evidently very satisfactory. We have had several patients in this laboratory in recent weeks who are under treatment with either warfarin or phenindione and whose thrombotest percentage has risen without apparent cause, indicating a considerable degree of underdosage. Before increasing their dose we questioned them about their diet and they admitted to having eaten chips cooked in this type of oil within the previous two or three days. When we were able to ensure that the oil was not used again, a repeat test done after 7 days or so showed a return to normal therapeutic values without alteration in the dose. This evidence is, of course, highly circumstantial, and a controlled trial is difficult to arrange, but the implications for treatment are obvious and so we feel justified in mentioning it in the hope that additional evidence may be forthcoming. to
Our thanks are due to the patient who first drew the substance in question.
Kingston and Long Grove Group Hospitals, Department of Pathology, Kingston upon Thames, Surrey.
our
attention
M. TALBOT B. W. MEADE.
J.
MEDICAL PROFESSION AS AN ELITE SIR,-Iwas intrigued by Dr. Lawless’s article (March 13, p. 543). I have two basic points to make. Firstly, Dr. Lawless apparently wants to further the cause of medical elitism by increasing the mysticism of cure, thus removing more of the individual’s responsibility for his own health. Surely, if a person’s health is primarily his own, treatment should be regarded as advice at the patient’s disposal. Treatment should not become so divorced from the person that the responsibility of his health has been captured and nullified by the doctor. James Lawless thinks otherwise, even going so far as to suggest that the patient’s dependence on the doctor is a useful means of manipulating society in socio-political fields. Thus, " The ranks of industrial managers ", he " says, should be full of doctors ". Secondly, his whole argument is based on one assumption, that " No community will operate without leaders ". In tune with the rest of the article, he does not simply mean an administrative bureaucracy but a manipulating leadership. To make such a presumption and base a whole argument on a factor influenced more by tradition and upbringing than by rational analysis is surely most unscientific. The concept relies on the ability of a superpower to remove power from the individual. If political apathy and undue tolerance of such problems as pollution, psychological alienation at work, and low medico-social standards is a characteristic of today, then this is perhaps due to sapping of the power of the individual to care for himself (and his health), and his domination by a superstructure that destroys any concept of a community which would engender a care for others. Dr. Lawless did, however, make a profound remark when he stated that " The medical schools teach the techniques of power ". Unfortunately this is very true. The whole patient/doctor relationship is still one of
blissful ignorance versus wealth-of-knowledge. It is sometimes pathetic to see patients’ unqualified acceptance of their treatment. This surely epitomises the level of subordination and lack of self-respect. The teaching of power techniques is also prevalent in the relationships between doctors, nurses, auxiliary staff, porters, and technicians. The medical student is permeated as much by his superias are the others by their inferiority. Both become victims of a system of antagonism between different groups, this maldistribution of power ultimately leading to greater inefficiency. I certainly agree that the medical profession has tended to be devoid of any overt politicism, but rather than utilise its " mysticism " as a dictatorial power it should surely apply its lifesaving abilities at the individual and com-
ority
munity levels. London SWll SEE.
MEDICAL STUDENT.
MUSCLE DISEASE IN CHRONIC ALCOHOLISM SIR,-Your editorial of June 5 (p. 1171) was read with great interest. Findings from a seven-year investigation of biochemical and genetic factors in 65 long-recovered and abstinent alcoholics 1,2indicate that in more than half there are disorders of carbohydrate metabolism manifested by abnormalities in blood-sugar level and serum lactate and pyruvate, and high urinary excretion of phosphate, nitrogen, aminoacids, and fermentable carbohydrates. Glucocorticosteroids are also significantly higher than normal,
particularly 17-OH oxogenic and 11-oxy-17-OH-corticosteroids. One of us (J. B.) previously reported prevalent in a group hypoglycxmia and flat glucose-tolerance curves of drinking or recently recovered alcoholics.33 These results suggest enzyme defects at some stage or stages in synthesis or breakdown of glycogen, the findings being similar in some respects to those in von Gierke’s disease or the Cori types.4 In such cases, where there exists serious deficiency of carbohydrate metabolites available to the Krebs cycle, it is understandable that increased compensatory demands should be made on aminoacids andprobably to a lesser extent-on fats for conversion to glucose or compounds such as aceto-acetate and pyruvate.’ Such demands, if chronic and excessive, must lead to protein breakdown affecting muscles and nerves after existing liver or tissue reserves have been depleted. Defects in the metabolism of tryptophan, with consequent shortage of endogenously synthesised nicotinamide, have also been found in the majority of the group.2 Since sugars and alcohol are both dependent on nicotinamide as N.A.D. coenzyme for metabolism, it is understandable that symptoms of myopathy and neuropathy (for example, excretion of myoglobin as reported) should be exacerbated after ingestion of alcohol which, in the favoured form of spirits, is devoid of vitamins. The importance of relationships between defects in carbohydrate metabolism and myopathy and neuropathy is amply illustrated by such diseases as untreated diabetes mellitus, beriberi (deficiency of thiamine), pellagra (deficiency of nicotinamide), and, indirectly, starvation and protein deficiency (kwashiorkor), where excessive demands are made on body protein. Similarly, protracted treatment with excessive doses of glucocorticosteroids may lead
myopathy. findings, in 6 cases of muscular dystrophy, of high urinary excretion of intermediate carbohydrate metabolites, including acetone, dihydroxyacetone, and glycerto
Recent
1. Rutter, L. F. J. Alc. 1968, 3, 51. 2. Rutter, L. F. ibid. 1970, 5, 91. 3. Benjafield, J. G., Moynihan, N. H. Practitioner, 4. Med. News Tribune, 1971, 3, no. 12, p. 1. 5. ibid. 1971, 3. no. 19, p. 5.
1967, 198, 552.
1293
aldehyde, together with excessive phosphate, urea, glucocorticoids, and peptide-like substances, suggest underlying relationship between defective carbohydrate metabolism and this disorder. Adetailedaccount of these and otherfindings and their relevance
to diagnostic tests in alcoholism
is in
Harley Street Laboratories, London W.1.
course
of preparation.
JOHN G. BENJAFIELD LAWRENCE F. RUTTER.
METABOLIC CHANGES AFTER PARATHYROIDECTOMY SIR,--Although acid-base abnormalities have been described in parathyroid disease,1-4 the role of parathyroid hormone in acid-base homoeostasis remains poorly defined.6 A recent experience is presented for discussion. A 67-year-old woman underwent successful surgical removal of a parathyroid adenoma after the discovery of persistent hypercalcasmia (serum-calcium 13-6-14-4 mg. per 100
STAFFING OF A NEW MATERNITY UNIT SIR,ňWe should like to draw attention to a very disquieting situation which has arisen regarding a new maternity unit which has been built at Heatherwood Hospital, Ascot, and which is due to open in a few months’ time. This was intended to be a completely integrated unit of 78 beds with full obstetric, psediatric, and anaathetic services. In line with all the latest views on such units, we believe that full obstetric cover must include the presence in the unit of a resident obstetric registrar at
A
ml.) by multiphasic laboratory screening.
skeletal survey revealed generalised demineralisation. There was no history of renal calculi. Prednisone, 20 mg. four times daily for 6 days, did not alter the serum-calcium levels. General anaesthesia, with halothane and succinylcholine, lasted 2 hours 15 minutes, during which time 1 litre of Ringer’s lactate with 200 mg. hydrocortisone was infused. The preoperative and postoperative electrolyte levels were as follows:
all times.
We,
as
representatives of all
the
general-practitioner on the maternity
obstetricians in this area, have served
liaison committee for the past two years, and have worked in principle all the detailed procedures for the new unit. The Ministry of Health has now informed us that it will not be creating any new registrar posts for this unit. We believe that two new registrars are required to provide sufficient cover, and that the absence of these will endanger the lives of our patients and will completely destroy the purpose behind an integrated maternity unit. We feel so strongly about this that we will not use the new unit until the situation is rectified. We believe that this view will be endorsed by all our local colleagues, and, unless there is some rapid rethinking on the matter, a serious and tragic situation is about to arise. G. W. COOK M. T. T. MORGAN MORGAN D. DRAKE-LEE MCKENDRICK McKENDRICK W. J. J. Ascot, E. T. FAUNCH FAuNcH B. J. RANSCOMBE. Berks. out
MANAGEMENT OF SYMPTOMLESS HYPERPARATHYROIDISM SIR,-The dilemma referred to by Mr. Gough and his colleagues (June 5, p. 1178) has existed previously in a different form, but will no doubt be increasingly recognised as more laboratories turn to chemical automation. As an example, an elderly, rather polysymptomatic, woman was kept under observation for a number of years, despite a firm diagnosis of parathyroid adenoma. Repeated medical and surgical reviews took the view that her symptoms were predominantly emotionally determined, and there was a strong suspicion that surgery might cure her biochemistry but not her clinical state. When she developed increased bone pain, an uneventful parathyroidectomy for adenoma was carried out by Mr. A. York Mason, with immediate relief of symptoms, including the emotional features. There must remain one doubt in pursuing a policy of continued observation of cases of chemical " parathyroid disease which are being kept under clinical and, in particular, renal review regularly. This uncertainty is that of the incidence of parathyroid crisis-a subject on which the published reports are singularly unhelpful. This would seem to be a useful subject for clinical investigation, and, were the facts clear, the dilemma referred to might well resolve itself into a waiting policy. "
St. Helier Hospital,
Carshalton, Surrey.
CEDRIC HIRSON.
By the second postoperative fallen to 9-2 mg. per 100 ml.
day the serum-calcium had
Unfortunately, serum-phosphorus determinations, which might have helped to elucidate the changes, were not made.
Postoperatively there was a fall in serum-potassium and compensated metabolic acidosis; a possible explanation is that potassium entered the cells in exchange for intracellular hydrogen ions. Perhaps a sudden decline in serumparathyroid-hormone levels played a role in these changes, in view of Wills’ hypothesis.5 Department of Medicine, Grant Hospital of Chicago, Chicago 60614.
CHARLES K. TASHIMA.
INFECTIOUS DISEASES IN SCHOOLS SIR,-Your editorial (June 5, p. 1171) states that a revised edition of the memorandum on this subject shrouds the responsibility for control in a fog of words. The booklet is meant for school doctors. Principal school medical officers are advised to prepare a simplified document for distribution to schools. To clear the air, let me state that it is absolutely untrue that " the medical officer with a special interest in the subject is likely to be frustrated by inadequate aid from the laboratory". Any school doctor who wishes to investigate an epidemic can get the help from the microbiologist in the Public Health Laboratory Service. Help has been available for a long time. Without it I could not have investigated an epidemic of whooping-cough in 1936 and proved that it was noninfectious at a comparatively early stage. Further back, I investigated an epidemic of Sonne dysentery and this stimulated my interest in diarrhoea and vomiting. These observations showed that the bacterial test for cure was unnecessary in adolescents. I agree wholeheartedly with the memorandum (paragraph 42) that these tests can be dispensed with, except in schools which have unsatisfactory sanitary arrangements. Heinemann, H. O. Metabolism, 1965, 17, 1137. Wills, M. R., McGowan, G. K. Br. med. J. 1964, i, 1153. Barzel, U. S. J. clin. Endocr. 1969, 29, 917 O’Grady, A. S., Morse, L. J., Lee, J. B. Ann. intern. Med. 63, 858. 5. Wills, M. R. Lancet, 1970, ii, 802.
1. 2. 3. 4.
1965
Letters
to
the Editor
EFFECT OF SILICONES ON THE ABSORPTION OF ANTICOAGULANT DRUGS SIR,-We wish to draw attention to the possible effect on the absorption of anticoagulant drugs of a substance allied to the silicones (methyl polysiloxane) which is present in certain proprietary brands of cooking oil as an additive. Its purpose is to give to potato chips an attractive crisp, dry appearance, for which it is evidently very satisfactory. We have had several patients in this laboratory in recent weeks who are under treatment with either warfarin or phenindione and whose thrombotest percentage has risen without apparent cause, indicating a considerable degree of underdosage. Before increasing their dose we questioned them about their diet and they admitted to having eaten chips cooked in this type of oil within the previous two or three days. When we were able to ensure that the oil was not used again, a repeat test done after 7 days or so showed a return to normal therapeutic values without alteration in the dose. This evidence is, of course, highly circumstantial, and a controlled trial is difficult to arrange, but the implications for treatment are obvious and so we feel justified in mentioning it in the hope that additional evidence may be forthcoming. to
Our thanks are due to the patient who first drew the substance in question.
Kingston and Long Grove Group Hospitals, Department of Pathology, Kingston upon Thames, Surrey.
our
attention
M. TALBOT B. W. MEADE.
J.
MEDICAL PROFESSION AS AN ELITE SIR,-Iwas intrigued by Dr. Lawless’s article (March 13, p. 543). I have two basic points to make. Firstly, Dr. Lawless apparently wants to further the cause of medical elitism by increasing the mysticism of cure, thus removing more of the individual’s responsibility for his own health. Surely, if a person’s health is primarily his own, treatment should be regarded as advice at the patient’s disposal. Treatment should not become so divorced from the person that the responsibility of his health has been captured and nullified by the doctor. James Lawless thinks otherwise, even going so far as to suggest that the patient’s dependence on the doctor is a useful means of manipulating society in socio-political fields. Thus, " The ranks of industrial managers ", he " says, should be full of doctors ". Secondly, his whole argument is based on one assumption, that " No community will operate without leaders ". In tune with the rest of the article, he does not simply mean an administrative bureaucracy but a manipulating leadership. To make such a presumption and base a whole argument on a factor influenced more by tradition and upbringing than by rational analysis is surely most unscientific. The concept relies on the ability of a superpower to remove power from the individual. If political apathy and undue tolerance of such problems as pollution, psychological alienation at work, and low medico-social standards is a characteristic of today, then this is perhaps due to sapping of the power of the individual to care for himself (and his health), and his domination by a superstructure that destroys any concept of a community which would engender a care for others. Dr. Lawless did, however, make a profound remark when he stated that " The medical schools teach the techniques of power ". Unfortunately this is very true. The whole patient/doctor relationship is still one of
blissful ignorance versus wealth-of-knowledge. It is sometimes pathetic to see patients’ unqualified acceptance of their treatment. This surely epitomises the level of subordination and lack of self-respect. The teaching of power techniques is also prevalent in the relationships between doctors, nurses, auxiliary staff, porters, and technicians. The medical student is permeated as much by his superias are the others by their inferiority. Both become victims of a system of antagonism between different groups, this maldistribution of power ultimately leading to greater inefficiency. I certainly agree that the medical profession has tended to be devoid of any overt politicism, but rather than utilise its " mysticism " as a dictatorial power it should surely apply its lifesaving abilities at the individual and com-
ority
munity levels. London SWll SEE.
MEDICAL STUDENT.
MUSCLE DISEASE IN CHRONIC ALCOHOLISM SIR,-Your editorial of June 5 (p. 1171) was read with great interest. Findings from a seven-year investigation of biochemical and genetic factors in 65 long-recovered and abstinent alcoholics 1,2indicate that in more than half there are disorders of carbohydrate metabolism manifested by abnormalities in blood-sugar level and serum lactate and pyruvate, and high urinary excretion of phosphate, nitrogen, aminoacids, and fermentable carbohydrates. Glucocorticosteroids are also significantly higher than normal,
particularly 17-OH oxogenic and 11-oxy-17-OH-corticosteroids. One of us (J. B.) previously reported prevalent in a group hypoglycxmia and flat glucose-tolerance curves of drinking or recently recovered alcoholics.33 These results suggest enzyme defects at some stage or stages in synthesis or breakdown of glycogen, the findings being similar in some respects to those in von Gierke’s disease or the Cori types.4 In such cases, where there exists serious deficiency of carbohydrate metabolites available to the Krebs cycle, it is understandable that increased compensatory demands should be made on aminoacids andprobably to a lesser extent-on fats for conversion to glucose or compounds such as aceto-acetate and pyruvate.’ Such demands, if chronic and excessive, must lead to protein breakdown affecting muscles and nerves after existing liver or tissue reserves have been depleted. Defects in the metabolism of tryptophan, with consequent shortage of endogenously synthesised nicotinamide, have also been found in the majority of the group.2 Since sugars and alcohol are both dependent on nicotinamide as N.A.D. coenzyme for metabolism, it is understandable that symptoms of myopathy and neuropathy (for example, excretion of myoglobin as reported) should be exacerbated after ingestion of alcohol which, in the favoured form of spirits, is devoid of vitamins. The importance of relationships between defects in carbohydrate metabolism and myopathy and neuropathy is amply illustrated by such diseases as untreated diabetes mellitus, beriberi (deficiency of thiamine), pellagra (deficiency of nicotinamide), and, indirectly, starvation and protein deficiency (kwashiorkor), where excessive demands are made on body protein. Similarly, protracted treatment with excessive doses of glucocorticosteroids may lead
myopathy. findings, in 6 cases of muscular dystrophy, of high urinary excretion of intermediate carbohydrate metabolites, including acetone, dihydroxyacetone, and glycerto
Recent
1. Rutter, L. F. J. Alc. 1968, 3, 51. 2. Rutter, L. F. ibid. 1970, 5, 91. 3. Benjafield, J. G., Moynihan, N. H. Practitioner, 4. Med. News Tribune, 1971, 3, no. 12, p. 1. 5. ibid. 1971, 3. no. 19, p. 5.
1967, 198, 552.
1293
aldehyde, together with excessive phosphate, urea, glucocorticoids, and peptide-like substances, suggest underlying relationship between defective carbohydrate metabolism and this disorder. Adetailedaccount of these and otherfindings and their relevance
to diagnostic tests in alcoholism
is in
Harley Street Laboratories, London W.1.
course
of preparation.
JOHN G. BENJAFIELD LAWRENCE F. RUTTER.
METABOLIC CHANGES AFTER PARATHYROIDECTOMY SIR,--Although acid-base abnormalities have been described in parathyroid disease,1-4 the role of parathyroid hormone in acid-base homoeostasis remains poorly defined.6 A recent experience is presented for discussion. A 67-year-old woman underwent successful surgical removal of a parathyroid adenoma after the discovery of persistent hypercalcasmia (serum-calcium 13-6-14-4 mg. per 100
STAFFING OF A NEW MATERNITY UNIT SIR,ňWe should like to draw attention to a very disquieting situation which has arisen regarding a new maternity unit which has been built at Heatherwood Hospital, Ascot, and which is due to open in a few months’ time. This was intended to be a completely integrated unit of 78 beds with full obstetric, psediatric, and anaathetic services. In line with all the latest views on such units, we believe that full obstetric cover must include the presence in the unit of a resident obstetric registrar at
A
ml.) by multiphasic laboratory screening.
skeletal survey revealed generalised demineralisation. There was no history of renal calculi. Prednisone, 20 mg. four times daily for 6 days, did not alter the serum-calcium levels. General anaesthesia, with halothane and succinylcholine, lasted 2 hours 15 minutes, during which time 1 litre of Ringer’s lactate with 200 mg. hydrocortisone was infused. The preoperative and postoperative electrolyte levels were as follows:
all times.
We,
as
representatives of all
the
general-practitioner on the maternity
obstetricians in this area, have served
liaison committee for the past two years, and have worked in principle all the detailed procedures for the new unit. The Ministry of Health has now informed us that it will not be creating any new registrar posts for this unit. We believe that two new registrars are required to provide sufficient cover, and that the absence of these will endanger the lives of our patients and will completely destroy the purpose behind an integrated maternity unit. We feel so strongly about this that we will not use the new unit until the situation is rectified. We believe that this view will be endorsed by all our local colleagues, and, unless there is some rapid rethinking on the matter, a serious and tragic situation is about to arise. G. W. COOK M. T. T. MORGAN MORGAN D. DRAKE-LEE MCKENDRICK McKENDRICK W. J. J. Ascot, E. T. FAUNCH FAuNcH B. J. RANSCOMBE. Berks. out
MANAGEMENT OF SYMPTOMLESS HYPERPARATHYROIDISM SIR,-The dilemma referred to by Mr. Gough and his colleagues (June 5, p. 1178) has existed previously in a different form, but will no doubt be increasingly recognised as more laboratories turn to chemical automation. As an example, an elderly, rather polysymptomatic, woman was kept under observation for a number of years, despite a firm diagnosis of parathyroid adenoma. Repeated medical and surgical reviews took the view that her symptoms were predominantly emotionally determined, and there was a strong suspicion that surgery might cure her biochemistry but not her clinical state. When she developed increased bone pain, an uneventful parathyroidectomy for adenoma was carried out by Mr. A. York Mason, with immediate relief of symptoms, including the emotional features. There must remain one doubt in pursuing a policy of continued observation of cases of chemical " parathyroid disease which are being kept under clinical and, in particular, renal review regularly. This uncertainty is that of the incidence of parathyroid crisis-a subject on which the published reports are singularly unhelpful. This would seem to be a useful subject for clinical investigation, and, were the facts clear, the dilemma referred to might well resolve itself into a waiting policy. "
St. Helier Hospital,
Carshalton, Surrey.
CEDRIC HIRSON.
By the second postoperative fallen to 9-2 mg. per 100 ml.
day the serum-calcium had
Unfortunately, serum-phosphorus determinations, which might have helped to elucidate the changes, were not made.
Postoperatively there was a fall in serum-potassium and compensated metabolic acidosis; a possible explanation is that potassium entered the cells in exchange for intracellular hydrogen ions. Perhaps a sudden decline in serumparathyroid-hormone levels played a role in these changes, in view of Wills’ hypothesis.5 Department of Medicine, Grant Hospital of Chicago, Chicago 60614.
CHARLES K. TASHIMA.
INFECTIOUS DISEASES IN SCHOOLS SIR,-Your editorial (June 5, p. 1171) states that a revised edition of the memorandum on this subject shrouds the responsibility for control in a fog of words. The booklet is meant for school doctors. Principal school medical officers are advised to prepare a simplified document for distribution to schools. To clear the air, let me state that it is absolutely untrue that " the medical officer with a special interest in the subject is likely to be frustrated by inadequate aid from the laboratory". Any school doctor who wishes to investigate an epidemic can get the help from the microbiologist in the Public Health Laboratory Service. Help has been available for a long time. Without it I could not have investigated an epidemic of whooping-cough in 1936 and proved that it was noninfectious at a comparatively early stage. Further back, I investigated an epidemic of Sonne dysentery and this stimulated my interest in diarrhoea and vomiting. These observations showed that the bacterial test for cure was unnecessary in adolescents. I agree wholeheartedly with the memorandum (paragraph 42) that these tests can be dispensed with, except in schools which have unsatisfactory sanitary arrangements. Heinemann, H. O. Metabolism, 1965, 17, 1137. Wills, M. R., McGowan, G. K. Br. med. J. 1964, i, 1153. Barzel, U. S. J. clin. Endocr. 1969, 29, 917 O’Grady, A. S., Morse, L. J., Lee, J. B. Ann. intern. Med. 63, 858. 5. Wills, M. R. Lancet, 1970, ii, 802.
1. 2. 3. 4.
1965