- Email: [email protected]
ASYMPTOMATIC HIATUS HERNIA
870
of society with science," and it is interesting that a large number of the proposed areas are of immediate concern to doctors: for example, the group might look at the allocation of scarce medical resources, genetic engineering and personality control, the confidentiality of personal data, and the testing of drugs and additives. At the inaugural meeting, Prof. J. Maynard Smith recalled that some years ago an informal discussion among scientists had ended with a general feeling that movements such as the B.S.S.R.S. would be of limited use because the outcome of research could not be predicted and because the use of science should be controlled by Parliament. If this negative attitude is less prevalent today (and the early support, from students and fellows of the Royal Society alike, for this new society suggests that it is) should we infer that these arguments are no longer valid? Certainly, it may be true to say that the uses or abuses of cloning in higher animals became problems immediately nuclear transplantation had been achieved in the frog, but many of those engaged in basic research cannot easily predict the practical outcome of much of their work. The B.S.S.R.S. is pledged to urge changes in public policy with regard to science and technology whenever the actual and potential social consequences of such policy seem undesirable, and to explore those developments which are likely to affect human life and its environment. It may find choosing the right topics at the right time one of its most difficult tasks. The B.S.S.R.S. does not claim that Parliament is no longer the place for making decisions on scientific matters; it does suggest, as have others, that the whole democratic process would benefit from being better informed scientifically. Lord Ritchie-Calder made out a strong case in a Royal Society of Arts lecture earlier this year 7" In a scientific age we need an informed democracy, not just hypnotized by the achievements of science or captivated, like children, by the gadgets, but capable of grass-root policies ". If the B.S.S.R.S. can contribute something to this end it will be serving a useful function. Certainly, the society deserves support from doctors, for much of what it is trying to do seems relevant to the problems associated with scientific medicine.
ment
INCONTINENCE
Centre in London organised a conference on incontinence last February, it was so heavily subscribed that a second was arranged on April 17, and this too was fully booked. Geriatricians, medical officers of health, general practitioners, urologists, hospital and public-health nurses, social workers, and members of several other professions were prepared to devote a whole day to the exchange of ideas on this often neglected topic; and that seems to indicate it is one of importance and concern. Yet how often is it discussed in practical terms ? The conference was planned jointly with the Disabled Living Activities Group of the Central Council for the Disabled, and the group’s chairman, Lady Hamilton, pointed out that a visitor from Mars might well think some of our ward layouts, furniture, and patients’ clothing were carefully designed to encourage incontinence. Lack of socially acceptable words for the excretory functions also made communication between doctor and patient difficult; and this point was taken up by Dr. G. L. Mills, who described an inquiry by the geriatric department of the Central Middlesex Hospital in a random WHEN the
Hospital
7. Ritchie-Calder.
Jl
R. Soc.
Arts, 1969, 117,
269.
sample of patients of pensionable age in two neighbouring practices. Of 63 people of pensionable age in 50 families, 22 (35%) had some difficulty in control of urination and defaecation (only 2 were persistently incontinent); and, of these 22, only the 2 truly incontinent patients had consulted their general practitioners. The reasons for inaction indicated prudishness, fatalism, and hopelessness. Worse still, of a sample of nurses and junior medical staff questioned about what advice they would give to an incontinent patient, only 2 out of 25 could give exact instructions; too often the reply was " you get some incontinence pads and things ". Dr. F. L. Willington, in a vivid description of the problems of incontinence in a rural area, demonstrated the deficiencies of most types of incontinence pads. Industrial research-workers were emphatic that insufficient use was being made of modern materials, that the principles of design were being flouted, and that great improvements were possible in incontinence pads and protective garments if only the medical and nursing professions would give a clear and full brief of what is required. The possibilities of prevention and early treatment by physiotherapy of stress incontinence and urgency were also stressed; some excellent results had been achieved by quite simple methods. These conferences reflected how much concern and interest there is in an affliction which causes more embarrassment and distress to patients than perhaps any other, and how much can be done by medical and nursing care, by attention to planning, furniture, clothing, and washing arrangements (bathrooms and lavatories must be warm and well lighted), by breaking down attitudes of prudery and awkwardness, and by overcoming the hopelessness that both professionals and patients are apt to feel in the face of incontinence. Moreover, far too little advantage has been taken of modern technological advances in the use of materials.
ASYMPTOMATIC HIATUS HERNIA
THE
radiological demonstration of hiatus hernia can exasperating problems for the physician and for the patient referred with dyspepsia. Some of the more puzzling features of the common sliding type of hernia are that gastro-oesophageal reflux can occur without causing create
symptoms, that reflux may be apparent without a demonstrable hernia,! and that many hernias exist without reflux} The common association of hiatus hernia with gallstones, diverticular disease, and duodenal ulcer further confuses the diagnostic situation, and the prudent physician will hesitate before attributing symptoms to this commonest of potential radiological red herrings. Some help may be gained from infusing hydrochloric acid into the gullet, for this will often provoke the pain associated with reflux,3 but it may also cause reflex myocardial ischmmia .4 From a study of 1011 patients with " gastro-oesophageal junctional disease " Palmerreported that about half of those with hiatus hernia or oesophagitis had no related symptoms and only a few (9%) complained of retrosternal burning pain associated with posture or the reflux of fluid into the mouth. The reported frequency of hiatus hernia varies widely; Hierbert, C. A., Belsey, R. H. R. J. thorac. cardiovasc. Surg. 1961, 42, 352. 2. Skinner, D. B., Camp, T. F. Aerospace Med. 1967, 38, 846. 3. Bennett, J. R., Atkinson, M. Gut, 1966, 7, 105. 4. Morris, J. C., Shelburne, P. F., Orgain, E. S. J. Am. med. Ass. 1963, 183, 788. 5. Palmer, E. D. Am. J. Med. 1968, 44, 566. See Lancet, 1968, ii, 267. 1.
871
and, with the development of radiological techniques which have progressively increased the stress on the hiatus, it is not surprising that increasing numbers have been-recorded. Two large series of consecutive bariummeal examinations gave rates of 7% 6 and 40%.7 Pridie8 examined 500 patients referred because of gastrointestinal symptoms and he found hiatus "hernias in 30%. "Dyer and Pridie 9 then investigated 95 symptom-free subjects selected over six months on the absence of complaints suggesting hiatus hernia; but 36 of them later admitted to minor gastrointestinal symptoms. The same radiowas followed in both series: patients logical technique were examined lying prone over a bolster after swallowing a glass of barium; and a hernia was diagnosed only if it could be demonstrated on a film taken after a short delay and if the mucosal folds in the hernial sac were continuous with those of the stomach. Of the 95 subjects examined, 33% had a hiatus hernia. All hernias were of the sliding variety, but reflux was apparent in only 5 cases and never in the absence of a hernia. Dyer and Pridie found no tendency for the frequency of hernia to increase with advancing age, and it seems that in symptom-free persons the oesophageal hiatus does not weaken as they grow older; nor was there any significant difference in sexdistribution, though the numbers were small and, by chance, twice as many men as women were included. More surprising was the lack of correlation with obesity; the association of weight gain and hiatus hernia seems to apply only to symptomatic cases, in which weight reduction is generally agreed to be a very effective means of controlling heartburn. The only valid conclusion that can be drawn from these findings is that the presence of a hiatus hernia bears an irregular and probably fortuitous relation to the prevalence of upper gastrointestinal symptoms. Of greater significance is the radiological demonstration of gastrooesophageal reflux, which is twice as common in symptomatic cases as in asymptomatic cases8 9; but more sensitive methods, such as the use of an indwelling pH electrode in the lower oesophagus, may be required.1O For the troubled minority of patients with hiatus hernia who find their way to hospital, it is clear that radiological investigation alone cannot always identify the point at which the physiological change has become pathological.
DOPA IN PARKINSON’S DISEASE
THE chemical substances thought to be concerned with neurotransmission within the central nervous system
include noradrenaline, dopamine, 5-hydroxytryptamine, acetylcholine, and y-aminobutyric acid. Noradrenaline and 5-hydroxytryptamine are found particularly in the hypothalamus, but dopamine is present in largest amounts in parts of the basal ganglia, particularly the striatum, putamen, and substantia nigra.l1 The concentration of
dopamine in significantly
these areas in reduced.12 13
patients with parkinsonism is Drugs which cause parkinsuch as sonism, reserpine, oc-methyldopa, cx-methyltyrosine, phenothiazines, and butyrophenone, all interfere with dopamine synthesis, storage, or activity within the brain. 6. 7. 8. 9. 10.
Conway-Hughes, J. H. L. Br. J. Radiol. 1956, 29, 331. Vandervelde, G. M., Carlson, H. C. Am. J. Roentg. 1964, 92, 989. Pridie, R. B. Gut, 1966, 7, 188. Dyer, N. H., Pridie, R. B. ibid. 1968, 9, 696. Morgan, E. H., Hill, L. D., Selby, D. K. Dis. Chest, 1963, 43, 367. 11. See Lancet, 1966, ii, 330. 12. Hornykiewicz, O. Wien. klin. Wschr. 1963, 75, 309. 13. Bernheimer, H., Hornykiewicz, O.Klin. Wschr. 1965, 43, 711.
Since there are postencephalitic, atherosclerotic, and idiopathic varieties of parkinsonism, the defect underlying the condition is probably complex. Nevertheless, it seemed logical to attempt treatment with dopamine in order to raise the level of the amine in the brain, and particularly in those areas where it was deficient. Dopamine given by mouth does not reach the central nervous system, however, so its immediate precursor has been used in several clinical trials. For example, Cotzias et al.14 noted striking and sustained improvement in some patients given D, L-dopa, provided that increases in dose were carefully monitored. But toxic effects, particularly reversible granulocytopenia, appeared, and the L-isomer, which is much less toxic, has therefore been used in later trials. Cotzias and his colleagues 15 have given slowly increasing oral doses of L-dopa to 28 patients with postencephalitic, atherosclerotic, and idiopathic parkinsonism in whom all other antiparkinsonian medication had been stopped. At least partial improvement was observed in all patients, but the extent to which each symptom and sign was affected varied from case to case. Some patients responded dramatically, but others only moderately. Akinesia was first improved, then rigidity, and finally tremor. Improvement in other features, such as shuffling, dysphagia, salivation, handwriting, posture, festination, and facial expression, was often striking but could not be fitted into any such sequence. Improvement was sustained for up to two years. Calne et al.16 studied 40 patients under institutional care for postencephalitic parkinsonism. They were given maximum tolerated doses of L-dopa, or placebo, for six weeks, using a betweensubject double-blind technique. Calne et al. were not so enthusiastic as Cotzia et al.15 about the results. Only 7 of the 20 patients receiving L-dopa improved substantially, and 3 moderately. 5 showed no useful response, and 5 had to stop treatment because of adverse effects. Placebo responses were surprisingly few among the 20 control patients: one patient developed abnormal movements, another became overactive, and 5 complained of giddiness. No sustained improvement was seen in patients
receiving placebo. There are certain differences between these trials which may contribute to the divergent conclusions. Cotzias et al. stopped all other antiparkinsonian treatment before giving L-dopa, whereas Calne et al. did not change previous treatment. Cotzias et al. found that 5-8 g. per day was the optimum daily dose, with a range of 4-2-7-5 g.; and Calne et al. gave an average of 1.3 g. per day, with a range of 0-5-2-5 g. as the maximum tolerated dose. The trial of Calne et al. was double-blind, while that of Cotzias et al. was not.
side-effects were common in both choreoathetoid movements, psychotic disturbances, anorexia, nausea and vomiting, and orthostatic hypotension. These reactions are themselves of interest. Apomorphine is an activator of dopamine receptors,!7 and it induces vomiting in man, and purposeless movements and vomiting in animals. The nausea and vomiting and the involuntary movements produced by L-dopa and by apomorphine may, therefore, have a common pharmacological basis. The cause of the ortho-
Dose-dependent trials-involuntary
14. 15. 16. 17.
Cotzias, G. C., Van Woert, M. H., Schiffer, L. M. New Engl. J. Med. 1967, 276, 374. Cotzias, G. C., Papavasiliov, P. S., Gellene, R. ibid. 1969, 280, 337. Calne, D. B., Stern, G. M., Laurence, D. R., Sharkey, J. Armitage, P. Lancet, April 12, 1969, p. 744. Andén, N. E., Rubenson, A., Fuxe, K., Hökfelt, T. J. Pharm. Pharmac. 1967, 19, 627.
of society with science," and it is interesting that a large number of the proposed areas are of immediate concern to doctors: for example, the group might look at the allocation of scarce medical resources, genetic engineering and personality control, the confidentiality of personal data, and the testing of drugs and additives. At the inaugural meeting, Prof. J. Maynard Smith recalled that some years ago an informal discussion among scientists had ended with a general feeling that movements such as the B.S.S.R.S. would be of limited use because the outcome of research could not be predicted and because the use of science should be controlled by Parliament. If this negative attitude is less prevalent today (and the early support, from students and fellows of the Royal Society alike, for this new society suggests that it is) should we infer that these arguments are no longer valid? Certainly, it may be true to say that the uses or abuses of cloning in higher animals became problems immediately nuclear transplantation had been achieved in the frog, but many of those engaged in basic research cannot easily predict the practical outcome of much of their work. The B.S.S.R.S. is pledged to urge changes in public policy with regard to science and technology whenever the actual and potential social consequences of such policy seem undesirable, and to explore those developments which are likely to affect human life and its environment. It may find choosing the right topics at the right time one of its most difficult tasks. The B.S.S.R.S. does not claim that Parliament is no longer the place for making decisions on scientific matters; it does suggest, as have others, that the whole democratic process would benefit from being better informed scientifically. Lord Ritchie-Calder made out a strong case in a Royal Society of Arts lecture earlier this year 7" In a scientific age we need an informed democracy, not just hypnotized by the achievements of science or captivated, like children, by the gadgets, but capable of grass-root policies ". If the B.S.S.R.S. can contribute something to this end it will be serving a useful function. Certainly, the society deserves support from doctors, for much of what it is trying to do seems relevant to the problems associated with scientific medicine.
ment
INCONTINENCE
Centre in London organised a conference on incontinence last February, it was so heavily subscribed that a second was arranged on April 17, and this too was fully booked. Geriatricians, medical officers of health, general practitioners, urologists, hospital and public-health nurses, social workers, and members of several other professions were prepared to devote a whole day to the exchange of ideas on this often neglected topic; and that seems to indicate it is one of importance and concern. Yet how often is it discussed in practical terms ? The conference was planned jointly with the Disabled Living Activities Group of the Central Council for the Disabled, and the group’s chairman, Lady Hamilton, pointed out that a visitor from Mars might well think some of our ward layouts, furniture, and patients’ clothing were carefully designed to encourage incontinence. Lack of socially acceptable words for the excretory functions also made communication between doctor and patient difficult; and this point was taken up by Dr. G. L. Mills, who described an inquiry by the geriatric department of the Central Middlesex Hospital in a random WHEN the
Hospital
7. Ritchie-Calder.
Jl
R. Soc.
Arts, 1969, 117,
269.
sample of patients of pensionable age in two neighbouring practices. Of 63 people of pensionable age in 50 families, 22 (35%) had some difficulty in control of urination and defaecation (only 2 were persistently incontinent); and, of these 22, only the 2 truly incontinent patients had consulted their general practitioners. The reasons for inaction indicated prudishness, fatalism, and hopelessness. Worse still, of a sample of nurses and junior medical staff questioned about what advice they would give to an incontinent patient, only 2 out of 25 could give exact instructions; too often the reply was " you get some incontinence pads and things ". Dr. F. L. Willington, in a vivid description of the problems of incontinence in a rural area, demonstrated the deficiencies of most types of incontinence pads. Industrial research-workers were emphatic that insufficient use was being made of modern materials, that the principles of design were being flouted, and that great improvements were possible in incontinence pads and protective garments if only the medical and nursing professions would give a clear and full brief of what is required. The possibilities of prevention and early treatment by physiotherapy of stress incontinence and urgency were also stressed; some excellent results had been achieved by quite simple methods. These conferences reflected how much concern and interest there is in an affliction which causes more embarrassment and distress to patients than perhaps any other, and how much can be done by medical and nursing care, by attention to planning, furniture, clothing, and washing arrangements (bathrooms and lavatories must be warm and well lighted), by breaking down attitudes of prudery and awkwardness, and by overcoming the hopelessness that both professionals and patients are apt to feel in the face of incontinence. Moreover, far too little advantage has been taken of modern technological advances in the use of materials.
ASYMPTOMATIC HIATUS HERNIA
THE
radiological demonstration of hiatus hernia can exasperating problems for the physician and for the patient referred with dyspepsia. Some of the more puzzling features of the common sliding type of hernia are that gastro-oesophageal reflux can occur without causing create
symptoms, that reflux may be apparent without a demonstrable hernia,! and that many hernias exist without reflux} The common association of hiatus hernia with gallstones, diverticular disease, and duodenal ulcer further confuses the diagnostic situation, and the prudent physician will hesitate before attributing symptoms to this commonest of potential radiological red herrings. Some help may be gained from infusing hydrochloric acid into the gullet, for this will often provoke the pain associated with reflux,3 but it may also cause reflex myocardial ischmmia .4 From a study of 1011 patients with " gastro-oesophageal junctional disease " Palmerreported that about half of those with hiatus hernia or oesophagitis had no related symptoms and only a few (9%) complained of retrosternal burning pain associated with posture or the reflux of fluid into the mouth. The reported frequency of hiatus hernia varies widely; Hierbert, C. A., Belsey, R. H. R. J. thorac. cardiovasc. Surg. 1961, 42, 352. 2. Skinner, D. B., Camp, T. F. Aerospace Med. 1967, 38, 846. 3. Bennett, J. R., Atkinson, M. Gut, 1966, 7, 105. 4. Morris, J. C., Shelburne, P. F., Orgain, E. S. J. Am. med. Ass. 1963, 183, 788. 5. Palmer, E. D. Am. J. Med. 1968, 44, 566. See Lancet, 1968, ii, 267. 1.
871
and, with the development of radiological techniques which have progressively increased the stress on the hiatus, it is not surprising that increasing numbers have been-recorded. Two large series of consecutive bariummeal examinations gave rates of 7% 6 and 40%.7 Pridie8 examined 500 patients referred because of gastrointestinal symptoms and he found hiatus "hernias in 30%. "Dyer and Pridie 9 then investigated 95 symptom-free subjects selected over six months on the absence of complaints suggesting hiatus hernia; but 36 of them later admitted to minor gastrointestinal symptoms. The same radiowas followed in both series: patients logical technique were examined lying prone over a bolster after swallowing a glass of barium; and a hernia was diagnosed only if it could be demonstrated on a film taken after a short delay and if the mucosal folds in the hernial sac were continuous with those of the stomach. Of the 95 subjects examined, 33% had a hiatus hernia. All hernias were of the sliding variety, but reflux was apparent in only 5 cases and never in the absence of a hernia. Dyer and Pridie found no tendency for the frequency of hernia to increase with advancing age, and it seems that in symptom-free persons the oesophageal hiatus does not weaken as they grow older; nor was there any significant difference in sexdistribution, though the numbers were small and, by chance, twice as many men as women were included. More surprising was the lack of correlation with obesity; the association of weight gain and hiatus hernia seems to apply only to symptomatic cases, in which weight reduction is generally agreed to be a very effective means of controlling heartburn. The only valid conclusion that can be drawn from these findings is that the presence of a hiatus hernia bears an irregular and probably fortuitous relation to the prevalence of upper gastrointestinal symptoms. Of greater significance is the radiological demonstration of gastrooesophageal reflux, which is twice as common in symptomatic cases as in asymptomatic cases8 9; but more sensitive methods, such as the use of an indwelling pH electrode in the lower oesophagus, may be required.1O For the troubled minority of patients with hiatus hernia who find their way to hospital, it is clear that radiological investigation alone cannot always identify the point at which the physiological change has become pathological.
DOPA IN PARKINSON’S DISEASE
THE chemical substances thought to be concerned with neurotransmission within the central nervous system
include noradrenaline, dopamine, 5-hydroxytryptamine, acetylcholine, and y-aminobutyric acid. Noradrenaline and 5-hydroxytryptamine are found particularly in the hypothalamus, but dopamine is present in largest amounts in parts of the basal ganglia, particularly the striatum, putamen, and substantia nigra.l1 The concentration of
dopamine in significantly
these areas in reduced.12 13
patients with parkinsonism is Drugs which cause parkinsuch as sonism, reserpine, oc-methyldopa, cx-methyltyrosine, phenothiazines, and butyrophenone, all interfere with dopamine synthesis, storage, or activity within the brain. 6. 7. 8. 9. 10.
Conway-Hughes, J. H. L. Br. J. Radiol. 1956, 29, 331. Vandervelde, G. M., Carlson, H. C. Am. J. Roentg. 1964, 92, 989. Pridie, R. B. Gut, 1966, 7, 188. Dyer, N. H., Pridie, R. B. ibid. 1968, 9, 696. Morgan, E. H., Hill, L. D., Selby, D. K. Dis. Chest, 1963, 43, 367. 11. See Lancet, 1966, ii, 330. 12. Hornykiewicz, O. Wien. klin. Wschr. 1963, 75, 309. 13. Bernheimer, H., Hornykiewicz, O.Klin. Wschr. 1965, 43, 711.
Since there are postencephalitic, atherosclerotic, and idiopathic varieties of parkinsonism, the defect underlying the condition is probably complex. Nevertheless, it seemed logical to attempt treatment with dopamine in order to raise the level of the amine in the brain, and particularly in those areas where it was deficient. Dopamine given by mouth does not reach the central nervous system, however, so its immediate precursor has been used in several clinical trials. For example, Cotzias et al.14 noted striking and sustained improvement in some patients given D, L-dopa, provided that increases in dose were carefully monitored. But toxic effects, particularly reversible granulocytopenia, appeared, and the L-isomer, which is much less toxic, has therefore been used in later trials. Cotzias and his colleagues 15 have given slowly increasing oral doses of L-dopa to 28 patients with postencephalitic, atherosclerotic, and idiopathic parkinsonism in whom all other antiparkinsonian medication had been stopped. At least partial improvement was observed in all patients, but the extent to which each symptom and sign was affected varied from case to case. Some patients responded dramatically, but others only moderately. Akinesia was first improved, then rigidity, and finally tremor. Improvement in other features, such as shuffling, dysphagia, salivation, handwriting, posture, festination, and facial expression, was often striking but could not be fitted into any such sequence. Improvement was sustained for up to two years. Calne et al.16 studied 40 patients under institutional care for postencephalitic parkinsonism. They were given maximum tolerated doses of L-dopa, or placebo, for six weeks, using a betweensubject double-blind technique. Calne et al. were not so enthusiastic as Cotzia et al.15 about the results. Only 7 of the 20 patients receiving L-dopa improved substantially, and 3 moderately. 5 showed no useful response, and 5 had to stop treatment because of adverse effects. Placebo responses were surprisingly few among the 20 control patients: one patient developed abnormal movements, another became overactive, and 5 complained of giddiness. No sustained improvement was seen in patients
receiving placebo. There are certain differences between these trials which may contribute to the divergent conclusions. Cotzias et al. stopped all other antiparkinsonian treatment before giving L-dopa, whereas Calne et al. did not change previous treatment. Cotzias et al. found that 5-8 g. per day was the optimum daily dose, with a range of 4-2-7-5 g.; and Calne et al. gave an average of 1.3 g. per day, with a range of 0-5-2-5 g. as the maximum tolerated dose. The trial of Calne et al. was double-blind, while that of Cotzias et al. was not.
side-effects were common in both choreoathetoid movements, psychotic disturbances, anorexia, nausea and vomiting, and orthostatic hypotension. These reactions are themselves of interest. Apomorphine is an activator of dopamine receptors,!7 and it induces vomiting in man, and purposeless movements and vomiting in animals. The nausea and vomiting and the involuntary movements produced by L-dopa and by apomorphine may, therefore, have a common pharmacological basis. The cause of the ortho-
Dose-dependent trials-involuntary
14. 15. 16. 17.
Cotzias, G. C., Van Woert, M. H., Schiffer, L. M. New Engl. J. Med. 1967, 276, 374. Cotzias, G. C., Papavasiliov, P. S., Gellene, R. ibid. 1969, 280, 337. Calne, D. B., Stern, G. M., Laurence, D. R., Sharkey, J. Armitage, P. Lancet, April 12, 1969, p. 744. Andén, N. E., Rubenson, A., Fuxe, K., Hökfelt, T. J. Pharm. Pharmac. 1967, 19, 627.