425 which cause odynophagia and oesophageal ulceration. The observations of Evans and Roberts suggest that the list will grow if endoscopy is done more frequently and earlier on in patients who complain of chest pain after swallowing tablets.
GASTRIC ACID OUTPUT BEFORE AND AFTER BROMOCRIPTINE IN
NINE MALE VOLUNTEERS
Gastrointestinal Unit,
Johannesburg Hospital, Johannesburg, South Africa
HYMIE KAVIN
INAPPROPRIATE ANTIHYPERTENSIVE THERAPY IN THE ELDERLY state that "in the preof atheromatous vessels with decreased elasticity it is possible that a major reduction in blood-pressure might critically decrease blood-flow". There is now considerable evidence to support this view. Autoregulation of the cerebral circulation is a homceostatic mechanism whereby cerebral blood-flow (C.B.F.) is maintained within normal limits over a wide range of systemic arterial pressure.2 In hypertensive patients3 and in baboons with experimentally induced hypertension5 autoregulation is adapted to a higher level of blood-pressure. This means that C.B.F. starts to decrease and symptoms of brain ischaemia begin at levels of blood-pressure that are well tolerated by normotensives. Thus there is less tolerance in the cerebral circulation to lowering the blood-pressure than in normotension. This may be even more likely in the elderly even though there is a lack of experimental evidence on this point. That over-treatment can cause a precipitate reduction in c.B.F. and induce ischaemic brain damage of cerebral perfusion failure type has also been described in two hypertensive patients. Even though cautious treatment of the type advocated by Jackson et al. can cause some reversal in the hypertensive autoregulatory curve, we would stress the need for caution when instituting treatment and the importance of titrating the dose of antihypertensive agent against the blood-pressure.
SIR,-Dr Jackson and his colleagues’
sence
University Department of Medical Cardiology, Royal Infirmary, Glasgow University Department of Neuropathology, Southern General Hospital, Glasgow
J. V. JONES D. I. GRAHAM
11
that the dopaminergic effect of bromocriptine would hav a similar effect. Further work is needed to confirm these observations, to elucidate the apparently biphasic stimulation of gastric acid output by bromocriptine and its duration, and to determine how this effect is mediated.
gastrin,"
I thank Dr M. A. Melvin of Sandoz Products Ltd, Captain J. Baxter and Corporal J. Bingham of the Royal Army Medical Corps, and the volunteers.
BROMOCRIPTINE AND GASTRIC ACID OUTPUT
significant side-effect of bromocriptine therapy,? especially larger doses needed in parkinsonism, and Wass et all have reported six cases of peptic ulcer, three with severe gastrointestinal haemorrhage, in patients treated with bromocriptine for acromegaly. The effect of bromocriptine on basal gastric acid output has been measured in nine male volunteers, aged 18-35 years, without a history of dyspepsia. The method was that used by Karim et al. 1U in their studies of prostaglandins and gastric acid SIR,-Nausea is
in suspension in 20 ml water at room temperature was instilled down the nasogastric tube. After 15 min the specimen of gastric juice collected was discarded. Collection of gastric juice was then continued in 15 min periods for 60 min. The specimens were assessed for volume (ml), acid concentration (mmol/1), and acid output (mmol), titrating to end-point pH 7 with 50 mmol/1 sodium hydroxide. Mean values for the nine men were calculated (table). In no respect are the mean increases found in gastric acid output statistically significant, but the number of subjects tested was small and an increase in mean basal acid output from 0.37 mmol/15 min to 1.05 mmol/15 min after bromocriptine instillation may explain the gastric side-effects of the drug and suggest caution in the use of this drug in patients with a history of peptic ulceration. I cannot explain how this effect of bromocriptine is mediated since dopamine is not known to increase gastric acid output. Indeed it might have been expected, from evidence that somatostatin reduces the gastric acid response to meals and penta-
powder
a
British Military Hospital, Münster, B.F.P.O. 17, West Germany
G. O. COWAN
with the
secretion. After
a
basal hour
collection, 2-5mg bromocriptine
2. 3.
Jackson, G., Pierscianowski, T. A., Mahon, W., Condon, J. Lancet, 1976, ii, 1317. Lassen, N. A. Physiol. Rev. 1959, 39, 183. Strandgaard, S., Olesen, J., Skinhoj, E., Lassen, N. A. Br. med. J. 1973, i,
4.
Strandgaard, S., Jones, J. V., Mackenzie,
1.
507. Res.
164.
E.
T., Harper, A. M. Circulation
1975, 37, Jones, J. V., Fitch, W., Mackenzie, E. T., Strandgaard, S., Harper, A. M. ibid. 1976, 39, 555. 6. Graham, D. I. Br. med. J. 1975, iv, 739. 7. Teychenne, P. F., Calne, D. B., Leigh, P. N., Greenacre, J. K., Reid, J. L., Petrie, A., Bamji, A. N. Lancet, 1975, ii, 473. 8 Kartzinel, R., Perlow, M., Teychenne, P., Gielen, A. C., Gillespie, M. M., Sadowsky, D. A., Calne, D. B. ibid. 1976, ii, 272. 9 Wass, J. A. H., Thorner, M. O., Besser, G. M., Morris, D., Mason, A. S., Liuzzi, A., Chiodini, P. G. ibid. p. 851. 10 Karim, S. M. M., Carter, D. C., Bhana, D., Ganesan, K. Br. med. J. 1973, 5.
i, 143
LYMPHOCYTE-TRANSFORMATION TEST IN DRUG ALLERGY
SIR,-Behan et al. 13 found signs of autoimmunity and depressed delayed hypersensitivity in vitro and in vivo in patients with the oculomucocutaneous syndrome associated with practolol therapy. They found that neither practolol nor two of its potential metabolites affected the transformation of lymphocytes derived from patients with this syndrome. Their-lymphocyte-transformation tests in vitro (L.T.T.) were done with
lymphocytes
obtained
during
However, the time of testing may be
a
the adverse reactions. determining factor in
outcome of the test. We have done sequential L.T.T.s in two patients with a hypersensitivity reaction to carbamazepine. An impaired response with phytohaemagglutinin and tuberculin and no transformation in the presence of carbamazepine were found during the reaction. About two months after the hyper-
the
D’Sa, A. A. J. B., Bloom, S. R., Baron, J. H. Lancet, 1975, i, 888. Gomez-Pan, A., Reed, J. D., Albinus, M., Shaw, B., Hall, R., Besser, G. M., Coy, D. H., Kastin, A. J., Schally, A. V. ibid. p. 886. 13. Behan, P. O., Behan, W. M. H., Zacharias, F. J., Nicholls, J. T. Lancet, 1976, ii, 984.
11. 12.
426
and the serum-calcium rose gradually to 8.6 mg/dl and remained normal when this treatment was discontinued. Serum-phosphorus values, which had been high at the beginning of this treatment (8-5mg/dl), fell to 6 mg/dl. At the same time the heart-rate fell to normal. It seems, therefore that the oral administration of 1a-OHD3 produced a beneficial effect on serum-calcium and on the heart-rate in a newborn with pro-
days,
tracted nenonatal
hypocaIcaEmia.
Aghia Sophia Children’s Hospital Institute of Child Health,
and
Athens 608, Greece
S. A. DOXIADIS P. D. LAPATSANIS
PLASMA-FIBRINOGEN, THROMBOEMBOLISM, AND HIP FRACTURES
Lymphocyte reactivity to carbamazepine (CBZ), phytohaemagglutinin (PHA), and tuberculin (PPD) during and after severe allergic reaction to CBZ in two patients. a higher L.T.T. with phytohaemagglutinin and tuberculin and transformation with carbamazepine were found (see figure). These findings were confirmed twice subsequently and with cryopreserved lymphocytes. To ensure that the L.T.T.s done by Behan et al. were not falsely negative because of impaired lymphocyte reactivity in the acute phase of the adverse reaction, they should have been repeated several months later. A positive L.T.T. with practolol or its metabolites might then have provided evidence of an allergic reaction to the drug.
sensitivity reaction, however,
Department of Medicine and Clinical Immunology Unit, University Hospital, Groningen, Netherlands
J. HOUWERZIJL G. C.
DE
GAST
1&agr;-HYDROXYVITAMIN D IN NEONATAL HYPOCALCÆMIA
SIR,-Kooh
et
al.’ described the beneficial effect of intra-
1a,25-dihydroxyvitamin D3 (la, 23[OH]Dg) on protracted neonatal hypocalcaemia. We report here a similar effect of the related compound 1a-OHD3 given orally to a newborn
venous
with the same condition. A male premature newborn (35 weeks’ gestation, birthweight 2300g) started twitching on the 5th day and a low serum-calcium was found (5-4 mg/dl). Intravenous calcium was given for 48 h (total dose 200 mg of calcium ion) and the value of serum-calcium rose to 7 mg/dl. The newborn was then given by mouth the same daily amount of calcium ions and 300 i.u. of vitamin D. The serum-calcium remained low, however, (6-6.5 mg/dl); the serum-25-OHD was normal (16 ng/ml); and the infant showed a heart-rate of 200 beats/min. We did not give any digitalis because this is considered dangerous in hypocalcaemic infants.23 We decided on the 14th day of life to give orally 1.5ng per day of 1-OH-D3 (kindly supplied by Dr S. Edelstein, Ichilov Hospital, Tel Aviv). This was given for 8 1. Kooh, S. W., Fraser, D., Toon, R., DeLuca, H. F. Lancet, 1976, 2. Chiswick, M. Br. med. J. 1972, iv, 364. 3. Aryampur, I., Farhoudi, A., Zangeneh, F. Am. J. Dis. Child. 1974,
ii,
1105.
129, 738.
SIR,-We have been following with interest the correspondence in your columns on plasma-fibrinogen and thromboembolism after myocardial infarction, and that on antithrombotic practice in the treatment of patients with hip fractures. While there seems little doubt that prophylactic oral anticoagulants after hip fracture reduce the incidence and extent of deep-vein thrombosis and practically abolish clinical and nec1 ropsy pulmonary embolism, why do so few orthopaedic surgeons in the United States3 and Britainuse these agents? Even if the convincing study of Morris and Mitche112 persuades surgeons of the efficacy of warfarin, two practical problems remain. Firstly, the incidence of bleeding is doubled by oral anticoagulants, 1which is not surprising in view of the trauma of hip fracture and of surgery, and the fact that most patients are females aged over 60-a population known tc have a high risk of bleeding during anticoagulant therapy.’ Secondly, the wide variation in susceptibility to oral anticoagulants demands regular control tests and individual daily dosage-a burden for busy orthopaedic wards. A high plasma-fibrinogen may be associated with venous thrombosis after surgeryb as well as after myocardial infarction.7 Plasma-fibrinogen is one determinant of blood viscosity, elevation of which before operation is also associated with postoperative thrombosis.8 If this high fibrinogen level plays any role in the pathogenesis of thrombosis, it is logical to attempt thrombotic prophylaxis by lowering the fibrinogen level to levels still compatible with haemostasis, which can be achieved with subcutaneous injections of ancrod (’Arvin’) as stated by Dr Sharp (Jan. 29, p. 251). We have reported that sustained, predictable depletion of plasma-fibrinogen after operation for hip fracture can be achieved with ancrod, given either by intravenousll or subcutaneous injection.lU Subcutaneous ancrod in fixed dosage seems a feasible regimen since only a single daily injection, requiring no special technique is required. In a preliminary study" plasma and blood viscosity were significantly reduced in parallel with fibrinogen depletion, and no increased bleeding or wound or fracture complications were seen. Since postoperative subcutaneous ancrod may be a simpler and safer prophylactic method than oral anticoagulants, we are assessing its antithrombotic potential in a controlled, double-blind trial in oatients with hin fractures. G. D. O. LOWE University Department of Medicine, C. D. FORBES Royal Infirmary, C. R. M. PRENTICE Glasgow G4 0SF 1. 2. 3. 4. 5.
Sevitt, S., Gallagher, N. G. Lancet, 1959, ii, 981. Morris, G. K., Mitchell, J. R. A. ibid. 1976, ii, 869. Simon, T. L., Stengle, J. M. Clin. Orthoped. rel. Res. 1974, 102, 181. Morris, G. K., Mitchell, J. R. A. Lancet, 1976, ii, 867. Jick, H., Slone, D., Borda, I. T., Shapiro, S. New Engl. J. Med. 1968, 279, 284.
G. P. Br. med. J. 1976, ii, 910. Fulton, R. M., Duckett, K. Lancet, 1976, ii, 1161. Dormandy, J. A., Edelman, J. B., Br. J. Surg. 1973, 60, 187. Barrie, W. W., Wood, E. H., Crumlish, P., Forbes, C. D., Prentice, C. R. M. Br. med. J. 1974, ii, 130. 10. Lowe, G. D. O., Morrice, J. J., Fulton, A., Forbes, C. D., Prentice, C. R. M., Barbenel, J. Br. J. Hœmat. 1976, 33, 609. 6. 7. 8. 9.
Clayton, J. K., Anderson, J. A., McNicol,
GASTRIC ACID OUTPUT BEFORE AND AFTER BROMOCRIPTINE IN
NINE MALE VOLUNTEERS
Gastrointestinal Unit,
Johannesburg Hospital, Johannesburg, South Africa
HYMIE KAVIN
INAPPROPRIATE ANTIHYPERTENSIVE THERAPY IN THE ELDERLY state that "in the preof atheromatous vessels with decreased elasticity it is possible that a major reduction in blood-pressure might critically decrease blood-flow". There is now considerable evidence to support this view. Autoregulation of the cerebral circulation is a homceostatic mechanism whereby cerebral blood-flow (C.B.F.) is maintained within normal limits over a wide range of systemic arterial pressure.2 In hypertensive patients3 and in baboons with experimentally induced hypertension5 autoregulation is adapted to a higher level of blood-pressure. This means that C.B.F. starts to decrease and symptoms of brain ischaemia begin at levels of blood-pressure that are well tolerated by normotensives. Thus there is less tolerance in the cerebral circulation to lowering the blood-pressure than in normotension. This may be even more likely in the elderly even though there is a lack of experimental evidence on this point. That over-treatment can cause a precipitate reduction in c.B.F. and induce ischaemic brain damage of cerebral perfusion failure type has also been described in two hypertensive patients. Even though cautious treatment of the type advocated by Jackson et al. can cause some reversal in the hypertensive autoregulatory curve, we would stress the need for caution when instituting treatment and the importance of titrating the dose of antihypertensive agent against the blood-pressure.
SIR,-Dr Jackson and his colleagues’
sence
University Department of Medical Cardiology, Royal Infirmary, Glasgow University Department of Neuropathology, Southern General Hospital, Glasgow
J. V. JONES D. I. GRAHAM
11
that the dopaminergic effect of bromocriptine would hav a similar effect. Further work is needed to confirm these observations, to elucidate the apparently biphasic stimulation of gastric acid output by bromocriptine and its duration, and to determine how this effect is mediated.
gastrin,"
I thank Dr M. A. Melvin of Sandoz Products Ltd, Captain J. Baxter and Corporal J. Bingham of the Royal Army Medical Corps, and the volunteers.
BROMOCRIPTINE AND GASTRIC ACID OUTPUT
significant side-effect of bromocriptine therapy,? especially larger doses needed in parkinsonism, and Wass et all have reported six cases of peptic ulcer, three with severe gastrointestinal haemorrhage, in patients treated with bromocriptine for acromegaly. The effect of bromocriptine on basal gastric acid output has been measured in nine male volunteers, aged 18-35 years, without a history of dyspepsia. The method was that used by Karim et al. 1U in their studies of prostaglandins and gastric acid SIR,-Nausea is
in suspension in 20 ml water at room temperature was instilled down the nasogastric tube. After 15 min the specimen of gastric juice collected was discarded. Collection of gastric juice was then continued in 15 min periods for 60 min. The specimens were assessed for volume (ml), acid concentration (mmol/1), and acid output (mmol), titrating to end-point pH 7 with 50 mmol/1 sodium hydroxide. Mean values for the nine men were calculated (table). In no respect are the mean increases found in gastric acid output statistically significant, but the number of subjects tested was small and an increase in mean basal acid output from 0.37 mmol/15 min to 1.05 mmol/15 min after bromocriptine instillation may explain the gastric side-effects of the drug and suggest caution in the use of this drug in patients with a history of peptic ulceration. I cannot explain how this effect of bromocriptine is mediated since dopamine is not known to increase gastric acid output. Indeed it might have been expected, from evidence that somatostatin reduces the gastric acid response to meals and penta-
powder
a
British Military Hospital, Münster, B.F.P.O. 17, West Germany
G. O. COWAN
with the
secretion. After
a
basal hour
collection, 2-5mg bromocriptine
2. 3.
Jackson, G., Pierscianowski, T. A., Mahon, W., Condon, J. Lancet, 1976, ii, 1317. Lassen, N. A. Physiol. Rev. 1959, 39, 183. Strandgaard, S., Olesen, J., Skinhoj, E., Lassen, N. A. Br. med. J. 1973, i,
4.
Strandgaard, S., Jones, J. V., Mackenzie,
1.
507. Res.
164.
E.
T., Harper, A. M. Circulation
1975, 37, Jones, J. V., Fitch, W., Mackenzie, E. T., Strandgaard, S., Harper, A. M. ibid. 1976, 39, 555. 6. Graham, D. I. Br. med. J. 1975, iv, 739. 7. Teychenne, P. F., Calne, D. B., Leigh, P. N., Greenacre, J. K., Reid, J. L., Petrie, A., Bamji, A. N. Lancet, 1975, ii, 473. 8 Kartzinel, R., Perlow, M., Teychenne, P., Gielen, A. C., Gillespie, M. M., Sadowsky, D. A., Calne, D. B. ibid. 1976, ii, 272. 9 Wass, J. A. H., Thorner, M. O., Besser, G. M., Morris, D., Mason, A. S., Liuzzi, A., Chiodini, P. G. ibid. p. 851. 10 Karim, S. M. M., Carter, D. C., Bhana, D., Ganesan, K. Br. med. J. 1973, 5.
i, 143
LYMPHOCYTE-TRANSFORMATION TEST IN DRUG ALLERGY
SIR,-Behan et al. 13 found signs of autoimmunity and depressed delayed hypersensitivity in vitro and in vivo in patients with the oculomucocutaneous syndrome associated with practolol therapy. They found that neither practolol nor two of its potential metabolites affected the transformation of lymphocytes derived from patients with this syndrome. Their-lymphocyte-transformation tests in vitro (L.T.T.) were done with
lymphocytes
obtained
during
However, the time of testing may be
a
the adverse reactions. determining factor in
outcome of the test. We have done sequential L.T.T.s in two patients with a hypersensitivity reaction to carbamazepine. An impaired response with phytohaemagglutinin and tuberculin and no transformation in the presence of carbamazepine were found during the reaction. About two months after the hyper-
the
D’Sa, A. A. J. B., Bloom, S. R., Baron, J. H. Lancet, 1975, i, 888. Gomez-Pan, A., Reed, J. D., Albinus, M., Shaw, B., Hall, R., Besser, G. M., Coy, D. H., Kastin, A. J., Schally, A. V. ibid. p. 886. 13. Behan, P. O., Behan, W. M. H., Zacharias, F. J., Nicholls, J. T. Lancet, 1976, ii, 984.
11. 12.
426
and the serum-calcium rose gradually to 8.6 mg/dl and remained normal when this treatment was discontinued. Serum-phosphorus values, which had been high at the beginning of this treatment (8-5mg/dl), fell to 6 mg/dl. At the same time the heart-rate fell to normal. It seems, therefore that the oral administration of 1a-OHD3 produced a beneficial effect on serum-calcium and on the heart-rate in a newborn with pro-
days,
tracted nenonatal
hypocaIcaEmia.
Aghia Sophia Children’s Hospital Institute of Child Health,
and
Athens 608, Greece
S. A. DOXIADIS P. D. LAPATSANIS
PLASMA-FIBRINOGEN, THROMBOEMBOLISM, AND HIP FRACTURES
Lymphocyte reactivity to carbamazepine (CBZ), phytohaemagglutinin (PHA), and tuberculin (PPD) during and after severe allergic reaction to CBZ in two patients. a higher L.T.T. with phytohaemagglutinin and tuberculin and transformation with carbamazepine were found (see figure). These findings were confirmed twice subsequently and with cryopreserved lymphocytes. To ensure that the L.T.T.s done by Behan et al. were not falsely negative because of impaired lymphocyte reactivity in the acute phase of the adverse reaction, they should have been repeated several months later. A positive L.T.T. with practolol or its metabolites might then have provided evidence of an allergic reaction to the drug.
sensitivity reaction, however,
Department of Medicine and Clinical Immunology Unit, University Hospital, Groningen, Netherlands
J. HOUWERZIJL G. C.
DE
GAST
1&agr;-HYDROXYVITAMIN D IN NEONATAL HYPOCALCÆMIA
SIR,-Kooh
et
al.’ described the beneficial effect of intra-
1a,25-dihydroxyvitamin D3 (la, 23[OH]Dg) on protracted neonatal hypocalcaemia. We report here a similar effect of the related compound 1a-OHD3 given orally to a newborn
venous
with the same condition. A male premature newborn (35 weeks’ gestation, birthweight 2300g) started twitching on the 5th day and a low serum-calcium was found (5-4 mg/dl). Intravenous calcium was given for 48 h (total dose 200 mg of calcium ion) and the value of serum-calcium rose to 7 mg/dl. The newborn was then given by mouth the same daily amount of calcium ions and 300 i.u. of vitamin D. The serum-calcium remained low, however, (6-6.5 mg/dl); the serum-25-OHD was normal (16 ng/ml); and the infant showed a heart-rate of 200 beats/min. We did not give any digitalis because this is considered dangerous in hypocalcaemic infants.23 We decided on the 14th day of life to give orally 1.5ng per day of 1-OH-D3 (kindly supplied by Dr S. Edelstein, Ichilov Hospital, Tel Aviv). This was given for 8 1. Kooh, S. W., Fraser, D., Toon, R., DeLuca, H. F. Lancet, 1976, 2. Chiswick, M. Br. med. J. 1972, iv, 364. 3. Aryampur, I., Farhoudi, A., Zangeneh, F. Am. J. Dis. Child. 1974,
ii,
1105.
129, 738.
SIR,-We have been following with interest the correspondence in your columns on plasma-fibrinogen and thromboembolism after myocardial infarction, and that on antithrombotic practice in the treatment of patients with hip fractures. While there seems little doubt that prophylactic oral anticoagulants after hip fracture reduce the incidence and extent of deep-vein thrombosis and practically abolish clinical and nec1 ropsy pulmonary embolism, why do so few orthopaedic surgeons in the United States3 and Britainuse these agents? Even if the convincing study of Morris and Mitche112 persuades surgeons of the efficacy of warfarin, two practical problems remain. Firstly, the incidence of bleeding is doubled by oral anticoagulants, 1which is not surprising in view of the trauma of hip fracture and of surgery, and the fact that most patients are females aged over 60-a population known tc have a high risk of bleeding during anticoagulant therapy.’ Secondly, the wide variation in susceptibility to oral anticoagulants demands regular control tests and individual daily dosage-a burden for busy orthopaedic wards. A high plasma-fibrinogen may be associated with venous thrombosis after surgeryb as well as after myocardial infarction.7 Plasma-fibrinogen is one determinant of blood viscosity, elevation of which before operation is also associated with postoperative thrombosis.8 If this high fibrinogen level plays any role in the pathogenesis of thrombosis, it is logical to attempt thrombotic prophylaxis by lowering the fibrinogen level to levels still compatible with haemostasis, which can be achieved with subcutaneous injections of ancrod (’Arvin’) as stated by Dr Sharp (Jan. 29, p. 251). We have reported that sustained, predictable depletion of plasma-fibrinogen after operation for hip fracture can be achieved with ancrod, given either by intravenousll or subcutaneous injection.lU Subcutaneous ancrod in fixed dosage seems a feasible regimen since only a single daily injection, requiring no special technique is required. In a preliminary study" plasma and blood viscosity were significantly reduced in parallel with fibrinogen depletion, and no increased bleeding or wound or fracture complications were seen. Since postoperative subcutaneous ancrod may be a simpler and safer prophylactic method than oral anticoagulants, we are assessing its antithrombotic potential in a controlled, double-blind trial in oatients with hin fractures. G. D. O. LOWE University Department of Medicine, C. D. FORBES Royal Infirmary, C. R. M. PRENTICE Glasgow G4 0SF 1. 2. 3. 4. 5.
Sevitt, S., Gallagher, N. G. Lancet, 1959, ii, 981. Morris, G. K., Mitchell, J. R. A. ibid. 1976, ii, 869. Simon, T. L., Stengle, J. M. Clin. Orthoped. rel. Res. 1974, 102, 181. Morris, G. K., Mitchell, J. R. A. Lancet, 1976, ii, 867. Jick, H., Slone, D., Borda, I. T., Shapiro, S. New Engl. J. Med. 1968, 279, 284.
G. P. Br. med. J. 1976, ii, 910. Fulton, R. M., Duckett, K. Lancet, 1976, ii, 1161. Dormandy, J. A., Edelman, J. B., Br. J. Surg. 1973, 60, 187. Barrie, W. W., Wood, E. H., Crumlish, P., Forbes, C. D., Prentice, C. R. M. Br. med. J. 1974, ii, 130. 10. Lowe, G. D. O., Morrice, J. J., Fulton, A., Forbes, C. D., Prentice, C. R. M., Barbenel, J. Br. J. Hœmat. 1976, 33, 609. 6. 7. 8. 9.
Clayton, J. K., Anderson, J. A., McNicol,
