370 LUNG INVOLVEMENT WITH ’VERDONE’
SIR,-A 38-year-old
woman
with
puerperal depression
was
admitted having swallowed, 1 hour previously, 40 ml of ’Verdone’ (I.C.I. selective weedkiller containing potassium salts of
2,4-dichlorophenoxyacetic and proprionic acids). She was fully conscious when washed out and there was no evidence of inhalation. Shortly afterwards she developed repeated haematemesis necessitating a two unit blood-transfusion. Nervous-system involvement consisted of drowsiness and tremors
initially
with
a
later
development
of
a
loss of bladder
sensation. Haematuria developed on the second day and lasted 24 h; plasma electrolytes, platelets, and clotting tests were normal. On the fourth day the patient had recurrent haemoptyses, was dyspnreic, and had crepitations in both lung bases. She was afebrile, with no clinical or electrocardiographic evidence of pulmonary emboli. Her nucleated cell count was 9-0x10/1 with a non-infected sputum. Chest X-rays showed patchy shadowing at both bases. Lung-function tests revealed a reduced forced vital capacity (F.v.c.) of 1.7 1 (predicted normal 2.9 1). Blood arterial gases on air were : Pao] 49.6 mmHg (6.6 kPa) and Paco] 32 mmHg (4.3kPa), and the blood pH was 7.42 (38 nmol H+/1). Over the next 4 days she improved with 35% oxygen. Blood gases and F.v.c. returned to normal (F.v.c. z91), and the chest X-rays gradually resolved. Throughout her stay in hospital liver-function tests, serum-glutamic-pyruvic-transaminase, and electrolytes remained within normal limits. The fatal dose of verdone is reported as greater than 45 ml.1 Ingestion of 2,4-dichlorophenoxyacetic acid produces epigastric pain, hsematemesis, tremor, convulsions, coma, renal failure, peripheral neuropathy, and severe skeletal muscle damage, while proprionic acid produces liver damage.2Lung involvement has not been previously reported with verdone.4 We suggest that lung involvement may occur with verdone but, unlike the lung damage in paraquat poisoning, it is reversible. We thank Dr T. M. Chalmers for Addenbrooke’s Hospital,
Trumpington Street, Cambridge
permission to report this
case.
M. K. DAVIES R. T. JUNG
PROSTHETIC MESOCAVAL SHUNTS IN PORTAL HYPERTENSION
SIR,-Several groups have commented favourably on the mesocaval shunt, using a ’Dacron’ prosthesis, as a therapeutic technique in portal hypertension.5-7 The accompanying table records the results of six shunts done at this hospital using either 18 or 19 mm knitted dacron grafts. A standard technique, as described by Drapanas et al.5 was used. Four of the 1. 2. 3. 4.
Guy’s Hospital Poisons Unit, London. Personal communication. Berwick, P. J. Am. med. Ass. 1970, 214, 1114. Gurd, M. R., Harmer, G. L. M., Lessel, B. Fd Cosmet. Tox. 1965, 3, 883. Imperial Chemical Industries, Central Toxicology Laboratory. Personal
5. 6. 7.
Drapanas, T., LoCicero, J., Dowling, J. B. Ann. Surg 1975, 181, 523. Giles, G. R., Brennan, T. G., Losowsky, M. S Br. J. Surg 1973, 60, 649. Smith, M., Tuft, R. J., Davidson, A. R., Laws, J. W, Dawson, J. L. Br med. J. 1974, iii, 705.
communication.
six patients re-bled, two in the first 14 days despite a satisfactory initial drop in portal pressure. One patient had evidence of recurrent pulmonary emboli possibly coming from thrombus within the shunt. The episode of septicaemia in the fifth patient and the subsequent clotting of this shunt underline the problems of introducing foreign materials into a bloodstream that is carrying gastrointestinal organisms. In only one case has the result been satisfactory. Our initial experience with this operation suggests that It carries with it considerable morbidity and mortality and that the end-to-side portacaval shunt is preferable. University Department of Surgery, Llandough Hospital, near Penarth, South Glamorgan CF6
J.
L. CRAVEN
D. J. T. WEBSTER 1XX
P. M. SMITH
CADMIUM AND HYPERTENSION
SIR,-Glauser et al.have presented
an interesting paper on controversial subject---cadmium and hypertension. The) state that Lener and Bibrz found that the liver and kidney cad mium content was much higher in patients who had beer hypertensive than in those who were normotensive, but Ixne and Bibr did not present data on liver levels of cadmium Others have tried to relate cadmium levels in tissues and bod fluids to hypertension. Morgan3 did not find differences i organ levels of cadmium between a group with hypertensiot and a control group. Webster4reported on plasma and urinar levels of cadmium in normotensives and hypertensives, andh did not find any differences. The influence of smoking on ac cumulation of cadmium is also relevant; this subject has bee! reviewed by Friberg et al. 16 Of special importance is the dii ference in blood-levels of cadmium among smokers and nor smokers: Ulander and Axelssonfound that the blood-cac mium was about 4 times higher in smokers than i a
non-smokers. Glauser et al.’ compared male and female normotensiv with male and female untreated hypertensives, the mean agl being 31 and 40 years, respectively. In studies of the type, ti groups compared are usually of the same sex and in a narrow age range. The mean age of their hypertensives was 39.7, m? a standard error of 4 and a number of 17, indicating that tl range must have been very wide. Glauser et al. claim that the groups are matched but th do not give enough details to substantiate this. They shou give individual data on sex, age, blood-pressure, smoki habits, and blood-cadmium. Furthermore, it would also be interest to have additional data on the health status of the { 1. Glauser, S. C., Bello, C. T., Glauser, E. M. Lancet, 1976, i, 717. 2. Lener, J., Bibr, B. ibid. 1971, i, 1970. 3. Morgan, J. M. Archs intern. Med. 1969, 123, 405. 4. Webster, P. O. Acta med. scand. 1973, 194, 505. 5. Friberg, L., Piscator, M., Nordberg, G., Kjellström, T. Cadmium in the En vironment. Cleveland, 1974. 6. Friberg, L., Kjellström, T., Nordberg, G., Piscator, M., Cadmium in the En vironment III. U.S. Environmental Protection Agency, Washington, D 1975. 7. Ulander, A., Axelsson, O. Lancet, 1974, i, 682.
RESULTS OF DACRON SHUNTS IN SIX CASES OF PORTAL HYPERTENSION
371
(e.g., the serum-creatinine levels in the hypertensives and normotensives). There is a need for more data on the relation between cadmium and hypertension in man, and the work of Glauser et al. would be of great value if they were to give uents
complete data.
Environmental Hygiene,
Department of Karolinska Institute,
MAGNUS PISCATOR
S-104 01 Stockholm 60, Sweden
It
This letter lows.-ED. L.
was
shown
to
Dr
Glauser, whose reply fol-
SIR,-Dr Piscator’s letter is welcome since it presents
an
opportunity define more precisely our patient population. This patient selection is crucial. Hypertensives whose disease was due to renovascular disease, phxochromocytoma, and aldosteronism were excluded from our study. Also excluded were patients with retinopathy, azot2emia, or left ventricular hypertrophy. Our patient population was thus comprised of patients that were hypertensive, had no demonstrable endorgan changes, had no detectable classical organic aetiology for their hypertension, and had received no previous therapy. This group is known from previous haemodynamic studies to have a high cardiac output and a normal total peripheral resistance. Once end-organ changes supervene there are many other processes that are not necessarily cadmium-related and the haemodynamic picture changes to that of high total peripheral resistance and at best normal cardiac output. Thus, we have chosen a population that is as close as possible to the initiating events of the hypertensive process. This patient selection might well account for any discrepancy between this study and previous studies. The control and hypertensive groups, as noted in the paper, had no significant difference with respect to age by the Student t-test on a group comparison of these two populations. Using a 2 x 2 contingency table we found no significant difference in distribution between males and females in the two groups. As noted above, neither controls nor hypertensives were azotaemic, the hypertensives being selected from that group which still had normal renal function. Urinary cadmium levels were not as discriminating in our hands as blood cadmium levels in differentiating normotensives from early essential hypertensives. The matter of urinary cadmium levels is unresolved: Wester’ did not find differences between normotensives and hypertensives whereas Perry and Schroeder2did find differences, We feel the blood cadmium level is biologically more significant and at least as good a discriminator as the urinary cadmium level. It is true and unfortunate that Lener and Bibr4 did not present data on the liver level of cadmium in human hypertensives, but concomitantly raised cadmium in the liver and kidney have been found in dogs, rats,6 and rabbits.7 One would hope ’. that in the near future the World Health Organisation8 will be ! able to rectify this deficit. In the discussion of the relation between cadmium levels and hypertension, the dose-dependent biphasic response of the mammalian organism to cadmium levels should be borne in mind. The results of Perry3 indicate that with chronic exposure to slightly raised cadmium levels one sees a hypertensive response due to an increase in cardiac output. Chronic expoto
i
1 Wester, P. O. Acta med. scand. 1973, 194, 505. 2 Perry, H. M., Schroeder, H. A. J. Lab. clin. Med. 1955, 46, 936. 3 Perry, H. M. in Trace Substances in Environmental Health-II (edited by D D. Hemphill); p. 101. Columbia, Missouri, 1968. 4 Lener. J. Bibr, B. Lancet, 1971, i, 970. 5 Byerrum, R. U., Anwar, R. A., Hoppert, C. A. J. Am. Water Works Ass. 1960, 52, 651. 6 Decker, L. E., Byerrum, R. U., Decker, C. F., Hoppert, C. A. Langham, R F Archs. ind. Hlth, 1958, 18, 228. 7 Fischer, G. M., Thind, G. S. Archs environ, Hlth, 1971, 23, 107. 8 Masironi, R. Trace Elements in Relation to Cardiovascular Disease. W.H.O. Offset Publication no. 5, Geneva, 1974.
high levels of cadmium does not produce hypertension. The same phenomena are seen in human beings, in whom modest elevation of cadmium leads to hypertension while severe cadmium toxicity is not associated with hypertension.9 Thus the dose of the cadmium and the duration of exposure are both crucial in determining what type of disease results from exposure to cadmium. In a set of experiments with previously untreated hypertensive patients, we have demonstrated a very significant drop in the blood cadmium levels into the normal range concomitant with a drop in the blood-pressure, systolic and diastolic, into the normal range for those hypertensive patients treated with a thiazide diuretic.’° These patients had no change in their smoking habits. sure to
Department of Pharmacology, Temple University Medical School,
Philadelphia, Pennsylvania 19140, S. C. GLAUSER
U.S.A.
PRESCRIBING IN GENERAL PRACTICE
SIR,-I found Dr Bliss’s article (July 31, p. 248) irritating, because her criticism of repeat prescriptions was invalid,
not
but because, like most G.P.s, I have heard it all before. For years I have been told in the medical Press that I do not know enough aoout, nor do enough for, mental illness, deafness, arthritis, or wife-beaters. I have been told one year that I must have an appointments system and the next that I must scrap it because it interferes with the patient’s access to medical care. Criticism of repeat prescriptions is at least twenty years old and has generated an excellent monograph" which would give Dr Bliss an insight into the reason for the repeat prescription and might temper her criticism of the way in which it is issued. The fact is that few people seem prepared to take the view, or at least investigate it rationally, that the general-practitioner service in its present form is a luxury that the ailing N.H.S. can no longer afford. One half of my workload is concerned with self-limiting minor illness for which the available treatments do not alter the natural history of the disease. Theorists of general practice advise us to refuse to deal with the "common cold", whereas the patient knows he has the right to see his doctor almost when and where he chooses. If he is denied this, the doctor can easily find himself the subject of an unpleasant complaint. Another quarter, perhaps, is spent diagnosing conditions that will have to be treated by other doctors, Why, for instance, does the unfortunate patient with a hernia have to come through me to be sent to a surgeon who will carry out an identical history and examination? The other quarter of the work may represent a real contribution to the welfare of the individual, providing that the G.P. is not so demoralised by the pressure of trivia that he no longer has the application to tackle the minority of his practice whom he can
really help. It must be apparent by now, after all the soul-searching that has been done on behalf of general practice, that the way the service is run is wasteful both of money and of men. Those who would reform it might find it profitable to ask first whether it is necessary to have general practitioners at all, rather than nibble at their more obvious shortcomings. And if the answer is that we are required, then it should be decided exactly what contribution we should be making to the public’s health and this part of the N.H.S. reformed in order to enable us to make it. The Surgery, Newport, Pembs. SA42 0TS 9. 10. 11.
J. C. BIGNALL
Tsuchiya, K. Keto J. Med. 1969, 18, 181. Glauser, E. M., Glauser, S. C., Bello, C. T. Pharmacologist, 1976, 18, 188. Balint, M., and others. Treatment or Diagnosis: a Study of Repeat Prescriptions in General Practice. London, 1970.
SIR,-A 38-year-old
woman
with
puerperal depression
was
admitted having swallowed, 1 hour previously, 40 ml of ’Verdone’ (I.C.I. selective weedkiller containing potassium salts of
2,4-dichlorophenoxyacetic and proprionic acids). She was fully conscious when washed out and there was no evidence of inhalation. Shortly afterwards she developed repeated haematemesis necessitating a two unit blood-transfusion. Nervous-system involvement consisted of drowsiness and tremors
initially
with
a
later
development
of
a
loss of bladder
sensation. Haematuria developed on the second day and lasted 24 h; plasma electrolytes, platelets, and clotting tests were normal. On the fourth day the patient had recurrent haemoptyses, was dyspnreic, and had crepitations in both lung bases. She was afebrile, with no clinical or electrocardiographic evidence of pulmonary emboli. Her nucleated cell count was 9-0x10/1 with a non-infected sputum. Chest X-rays showed patchy shadowing at both bases. Lung-function tests revealed a reduced forced vital capacity (F.v.c.) of 1.7 1 (predicted normal 2.9 1). Blood arterial gases on air were : Pao] 49.6 mmHg (6.6 kPa) and Paco] 32 mmHg (4.3kPa), and the blood pH was 7.42 (38 nmol H+/1). Over the next 4 days she improved with 35% oxygen. Blood gases and F.v.c. returned to normal (F.v.c. z91), and the chest X-rays gradually resolved. Throughout her stay in hospital liver-function tests, serum-glutamic-pyruvic-transaminase, and electrolytes remained within normal limits. The fatal dose of verdone is reported as greater than 45 ml.1 Ingestion of 2,4-dichlorophenoxyacetic acid produces epigastric pain, hsematemesis, tremor, convulsions, coma, renal failure, peripheral neuropathy, and severe skeletal muscle damage, while proprionic acid produces liver damage.2Lung involvement has not been previously reported with verdone.4 We suggest that lung involvement may occur with verdone but, unlike the lung damage in paraquat poisoning, it is reversible. We thank Dr T. M. Chalmers for Addenbrooke’s Hospital,
Trumpington Street, Cambridge
permission to report this
case.
M. K. DAVIES R. T. JUNG
PROSTHETIC MESOCAVAL SHUNTS IN PORTAL HYPERTENSION
SIR,-Several groups have commented favourably on the mesocaval shunt, using a ’Dacron’ prosthesis, as a therapeutic technique in portal hypertension.5-7 The accompanying table records the results of six shunts done at this hospital using either 18 or 19 mm knitted dacron grafts. A standard technique, as described by Drapanas et al.5 was used. Four of the 1. 2. 3. 4.
Guy’s Hospital Poisons Unit, London. Personal communication. Berwick, P. J. Am. med. Ass. 1970, 214, 1114. Gurd, M. R., Harmer, G. L. M., Lessel, B. Fd Cosmet. Tox. 1965, 3, 883. Imperial Chemical Industries, Central Toxicology Laboratory. Personal
5. 6. 7.
Drapanas, T., LoCicero, J., Dowling, J. B. Ann. Surg 1975, 181, 523. Giles, G. R., Brennan, T. G., Losowsky, M. S Br. J. Surg 1973, 60, 649. Smith, M., Tuft, R. J., Davidson, A. R., Laws, J. W, Dawson, J. L. Br med. J. 1974, iii, 705.
communication.
six patients re-bled, two in the first 14 days despite a satisfactory initial drop in portal pressure. One patient had evidence of recurrent pulmonary emboli possibly coming from thrombus within the shunt. The episode of septicaemia in the fifth patient and the subsequent clotting of this shunt underline the problems of introducing foreign materials into a bloodstream that is carrying gastrointestinal organisms. In only one case has the result been satisfactory. Our initial experience with this operation suggests that It carries with it considerable morbidity and mortality and that the end-to-side portacaval shunt is preferable. University Department of Surgery, Llandough Hospital, near Penarth, South Glamorgan CF6
J.
L. CRAVEN
D. J. T. WEBSTER 1XX
P. M. SMITH
CADMIUM AND HYPERTENSION
SIR,-Glauser et al.have presented
an interesting paper on controversial subject---cadmium and hypertension. The) state that Lener and Bibrz found that the liver and kidney cad mium content was much higher in patients who had beer hypertensive than in those who were normotensive, but Ixne and Bibr did not present data on liver levels of cadmium Others have tried to relate cadmium levels in tissues and bod fluids to hypertension. Morgan3 did not find differences i organ levels of cadmium between a group with hypertensiot and a control group. Webster4reported on plasma and urinar levels of cadmium in normotensives and hypertensives, andh did not find any differences. The influence of smoking on ac cumulation of cadmium is also relevant; this subject has bee! reviewed by Friberg et al. 16 Of special importance is the dii ference in blood-levels of cadmium among smokers and nor smokers: Ulander and Axelssonfound that the blood-cac mium was about 4 times higher in smokers than i a
non-smokers. Glauser et al.’ compared male and female normotensiv with male and female untreated hypertensives, the mean agl being 31 and 40 years, respectively. In studies of the type, ti groups compared are usually of the same sex and in a narrow age range. The mean age of their hypertensives was 39.7, m? a standard error of 4 and a number of 17, indicating that tl range must have been very wide. Glauser et al. claim that the groups are matched but th do not give enough details to substantiate this. They shou give individual data on sex, age, blood-pressure, smoki habits, and blood-cadmium. Furthermore, it would also be interest to have additional data on the health status of the { 1. Glauser, S. C., Bello, C. T., Glauser, E. M. Lancet, 1976, i, 717. 2. Lener, J., Bibr, B. ibid. 1971, i, 1970. 3. Morgan, J. M. Archs intern. Med. 1969, 123, 405. 4. Webster, P. O. Acta med. scand. 1973, 194, 505. 5. Friberg, L., Piscator, M., Nordberg, G., Kjellström, T. Cadmium in the En vironment. Cleveland, 1974. 6. Friberg, L., Kjellström, T., Nordberg, G., Piscator, M., Cadmium in the En vironment III. U.S. Environmental Protection Agency, Washington, D 1975. 7. Ulander, A., Axelsson, O. Lancet, 1974, i, 682.
RESULTS OF DACRON SHUNTS IN SIX CASES OF PORTAL HYPERTENSION
371
(e.g., the serum-creatinine levels in the hypertensives and normotensives). There is a need for more data on the relation between cadmium and hypertension in man, and the work of Glauser et al. would be of great value if they were to give uents
complete data.
Environmental Hygiene,
Department of Karolinska Institute,
MAGNUS PISCATOR
S-104 01 Stockholm 60, Sweden
It
This letter lows.-ED. L.
was
shown
to
Dr
Glauser, whose reply fol-
SIR,-Dr Piscator’s letter is welcome since it presents
an
opportunity define more precisely our patient population. This patient selection is crucial. Hypertensives whose disease was due to renovascular disease, phxochromocytoma, and aldosteronism were excluded from our study. Also excluded were patients with retinopathy, azot2emia, or left ventricular hypertrophy. Our patient population was thus comprised of patients that were hypertensive, had no demonstrable endorgan changes, had no detectable classical organic aetiology for their hypertension, and had received no previous therapy. This group is known from previous haemodynamic studies to have a high cardiac output and a normal total peripheral resistance. Once end-organ changes supervene there are many other processes that are not necessarily cadmium-related and the haemodynamic picture changes to that of high total peripheral resistance and at best normal cardiac output. Thus, we have chosen a population that is as close as possible to the initiating events of the hypertensive process. This patient selection might well account for any discrepancy between this study and previous studies. The control and hypertensive groups, as noted in the paper, had no significant difference with respect to age by the Student t-test on a group comparison of these two populations. Using a 2 x 2 contingency table we found no significant difference in distribution between males and females in the two groups. As noted above, neither controls nor hypertensives were azotaemic, the hypertensives being selected from that group which still had normal renal function. Urinary cadmium levels were not as discriminating in our hands as blood cadmium levels in differentiating normotensives from early essential hypertensives. The matter of urinary cadmium levels is unresolved: Wester’ did not find differences between normotensives and hypertensives whereas Perry and Schroeder2did find differences, We feel the blood cadmium level is biologically more significant and at least as good a discriminator as the urinary cadmium level. It is true and unfortunate that Lener and Bibr4 did not present data on the liver level of cadmium in human hypertensives, but concomitantly raised cadmium in the liver and kidney have been found in dogs, rats,6 and rabbits.7 One would hope ’. that in the near future the World Health Organisation8 will be ! able to rectify this deficit. In the discussion of the relation between cadmium levels and hypertension, the dose-dependent biphasic response of the mammalian organism to cadmium levels should be borne in mind. The results of Perry3 indicate that with chronic exposure to slightly raised cadmium levels one sees a hypertensive response due to an increase in cardiac output. Chronic expoto
i
1 Wester, P. O. Acta med. scand. 1973, 194, 505. 2 Perry, H. M., Schroeder, H. A. J. Lab. clin. Med. 1955, 46, 936. 3 Perry, H. M. in Trace Substances in Environmental Health-II (edited by D D. Hemphill); p. 101. Columbia, Missouri, 1968. 4 Lener. J. Bibr, B. Lancet, 1971, i, 970. 5 Byerrum, R. U., Anwar, R. A., Hoppert, C. A. J. Am. Water Works Ass. 1960, 52, 651. 6 Decker, L. E., Byerrum, R. U., Decker, C. F., Hoppert, C. A. Langham, R F Archs. ind. Hlth, 1958, 18, 228. 7 Fischer, G. M., Thind, G. S. Archs environ, Hlth, 1971, 23, 107. 8 Masironi, R. Trace Elements in Relation to Cardiovascular Disease. W.H.O. Offset Publication no. 5, Geneva, 1974.
high levels of cadmium does not produce hypertension. The same phenomena are seen in human beings, in whom modest elevation of cadmium leads to hypertension while severe cadmium toxicity is not associated with hypertension.9 Thus the dose of the cadmium and the duration of exposure are both crucial in determining what type of disease results from exposure to cadmium. In a set of experiments with previously untreated hypertensive patients, we have demonstrated a very significant drop in the blood cadmium levels into the normal range concomitant with a drop in the blood-pressure, systolic and diastolic, into the normal range for those hypertensive patients treated with a thiazide diuretic.’° These patients had no change in their smoking habits. sure to
Department of Pharmacology, Temple University Medical School,
Philadelphia, Pennsylvania 19140, S. C. GLAUSER
U.S.A.
PRESCRIBING IN GENERAL PRACTICE
SIR,-I found Dr Bliss’s article (July 31, p. 248) irritating, because her criticism of repeat prescriptions was invalid,
not
but because, like most G.P.s, I have heard it all before. For years I have been told in the medical Press that I do not know enough aoout, nor do enough for, mental illness, deafness, arthritis, or wife-beaters. I have been told one year that I must have an appointments system and the next that I must scrap it because it interferes with the patient’s access to medical care. Criticism of repeat prescriptions is at least twenty years old and has generated an excellent monograph" which would give Dr Bliss an insight into the reason for the repeat prescription and might temper her criticism of the way in which it is issued. The fact is that few people seem prepared to take the view, or at least investigate it rationally, that the general-practitioner service in its present form is a luxury that the ailing N.H.S. can no longer afford. One half of my workload is concerned with self-limiting minor illness for which the available treatments do not alter the natural history of the disease. Theorists of general practice advise us to refuse to deal with the "common cold", whereas the patient knows he has the right to see his doctor almost when and where he chooses. If he is denied this, the doctor can easily find himself the subject of an unpleasant complaint. Another quarter, perhaps, is spent diagnosing conditions that will have to be treated by other doctors, Why, for instance, does the unfortunate patient with a hernia have to come through me to be sent to a surgeon who will carry out an identical history and examination? The other quarter of the work may represent a real contribution to the welfare of the individual, providing that the G.P. is not so demoralised by the pressure of trivia that he no longer has the application to tackle the minority of his practice whom he can
really help. It must be apparent by now, after all the soul-searching that has been done on behalf of general practice, that the way the service is run is wasteful both of money and of men. Those who would reform it might find it profitable to ask first whether it is necessary to have general practitioners at all, rather than nibble at their more obvious shortcomings. And if the answer is that we are required, then it should be decided exactly what contribution we should be making to the public’s health and this part of the N.H.S. reformed in order to enable us to make it. The Surgery, Newport, Pembs. SA42 0TS 9. 10. 11.
J. C. BIGNALL
Tsuchiya, K. Keto J. Med. 1969, 18, 181. Glauser, E. M., Glauser, S. C., Bello, C. T. Pharmacologist, 1976, 18, 188. Balint, M., and others. Treatment or Diagnosis: a Study of Repeat Prescriptions in General Practice. London, 1970.
