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MALIGNANT MELANOMA OF THE SKIN
602 Neither of the cases so far reported has had autoradiographic studies, so that absolute identity of the chromosome remains In view of their obvious value in helping to uncertain. distinguish between chromosomes of similar structure such studies should be carried out in these patients. A specific label of the type " partial (or complete) monosomy G21 (or G22) " may then be applied instead of the rather misleading term given. Dr. Court Brown and his colleagues refer also to a very close similarity between the craniofacial features in the patient of Dr. Reisman and his colleagues and those in Potter’s syndrome (renal agenesis). The illustrations of this syndrome by Pottery and Macgregor,4do not resemble closely the patient of Dr. Reisman and his colleagues. Other photographs of typical cases of renal agenesis have been published5 in which normal chromosome patterns were also observed. Furthermore, patients with renal agenesis usually survive only a matter of hours or are stillbirths, but neither case of partial G monosomy has succumbed so far. Therefore the implication that the patient of Dr. Reisman and his colleagues could have a balanced chromosome rearrangement with an undetectable translocation, coupled with Potter’s syndrome, is not well founded. Queen Elizabeth Hospital For Children, L. BUTLER. London. E.2.
J.
SIR,-In reply to the comments of Dr. Court Brown and colleagues on our report of the infant with " antimongolism ", we certainly do endorse the opinion that family his
studies are necessary. In this regard, our error was one of omission rather than that of commission, since chromosome studies had been performed on both parents, and their karyotypes were apparently normal. Since we do feel strongly about the need for the investigation of the parents of children with chromosomal abnormalities, we are now routinely investigating all the parents in the younger age-group who have had children with Down’s syndrome and other chromosomal aberrations. University of Louisville School of Medicine, Louisville, Kentucky, U.S.A.
SBRUM-VITAMIN-B12
LEVELS AND RECOVERY OF ADDED
VITAMIN-B12
IN
10 PATIENTS RECEIVING CHLORPROMAZINE
doses of chlorpromazine for several weeks before the sera were collected. We also added 100 pg. per ml. of vitamin-B12 to 6 of the sera, and 200 pg. per ml. to 3 of the sera, in order to determine whether the vitamin could be recovered in the assay. The results, summarised in the accompanying table, show that the serum-vitamin-B is levels were normal in all the patients, and that between 75% and 125% of the vitamin-Bl2 added to the sera was recovered. We have obtained a similar range of recovery of vitamin-B12 added to normal sera. In another experiment we observed that the addition of chlorpromazine to normal serum (1 mg. per ml.) did not affect the result of the vitamin-B12 assay. We can conclude from these results that chlorpromazine does not suppress the growth of L. leichmanii. JOHN FORSHAW Sefton General Hospital, LILIAN HARWOOD. Liverpool, 15.
MALIGNANT MELANOMA OF THE SKIN SIR,-While there is much in your leaderwith which I agree, I must take you to task on such a dogmatic statement as: Doubt can no longer exist that local excision of a malignant melanoma should be followed by prophylactic dissection of the regional nodes." Prophylactic is a poor term to use, since the operation does nothing to prevent disease. In some cases it removes subclinical deposits, but whether this adds to the comfort or survival of the individual patient is still not clearly settled. The principal article2 cited in support of your contention suffers, as do most if not all series of any size, in being neither controlled nor presented in a form which can be compared with similar series which are not electively treated. The presentation of results according to the pathological report can distort the figures, as I have shown.3 In addition, Mundth et al. estimated survival from the time of onset of diseasesurely a less than satisfactory index, depending as it does on "
LEONARD E. REISMAN.
"
SERUM-VITAMIN-B12 AND CHLORPROMAZINE SIR,-We have read with interest the article by Dr. Herbert and his colleagues6 in which they show that low Euglena gracilis serum-vitamin-B12 levels in patients receiving chlorpromazine therapy are an artefact. It should be pointed out, however, that their coated-charcoal assay, which was not affected by chlorpromazine, is an expensive method. In their
"
report of this method Herbert and his colleagues ’7 describe the use of 57Co-vitamin-B12 with a specific activity of 11 -.C per {l.g.; the approximate cost of this radioactive isotope would be C40 for the first serum-assay in each batch, and E20 for memory, and not record. Mundth et al. presented, not true each other serum-assay.8 Later (in 1965) Herbert 9 has stated ten-year survival figures, but those from patients who were that the 57Co-vitamin-B12 may have a specific activity as low followed up for between five and ten years. Over a quarter of as 1 jjt.C per {l.g., but he recommends 4 {iC per {ig. as the best cases were not used in their calculations; they died of specific activity to use. But, even if 5’Co-vitamin-Bl, with a their other (unstated) or were lost to follow-up. One of their specific activity of 1 {l.C per {l.g. were used, the cost of the tables causes is arithmetically incorrect on cross-checking, and the radioactive isotope would be roughly E4 for the first serumstandard errors are in many cases so high and the total numbers assay in a bath, and E2 for each other assay. so low that few firm conclusions should be drawn. Thus their In view of the fairly low cost of the Lactobacillus leichmanii " prophylactically " dissected positive-node group totals 18 serum-vitamin-B12 assay we considered that it was important cases, of which 5 were at some stage excluded from the to determine whether the results obtained with this method calculation. were affected by chlorpromazine therapy. We have therefore To cite only the percentage results from such reports lends the levels the L. leichmanii assayed by serum-vitamin-B12 a spurious air of statistical significance. To compare the method in 10 psychiatric patients on chlorpromazine therapy. of and positive on survivals those whose nodes were negative With one exception (no. 8) the patients had been taking large elective with those who eventually or initially required operation 3. Potter, E. L. Pathology of the Fetus and the Infant; p. 430. Chicago, 1961. dissection for clinically and histologically positive nodes invites 4. Macgregor, A. R. Pathology of Infancy and Childhood; p. 214. Edinburgh, 1960. the question: " What happened to those who had no elective 5. Passarge, E., Sutherland, J. M. Am. J. Dis. Child. 1965, 109, 80. " treatment and did not require dissection ? 6. Herbert, V., Gottlieb, C. W., Altschule, M. D. Lancet, 1965, ii, 1052. 7. Lau, K.-S., Gottlieb, C., Wasserman, L. R., Herbert, V. Blood, 1965, It seems to be impossible to persuade surgical centres of any 202. 8.
26, Catalogue of Radio-active products, Radiochemical Centre, Amersham, 1965-66; p. 75.
9.
Herbert, V. Personal communication.
1. Lancet, 1965, ii, 1171. 2. Mundth, E. D., Guralnick, E. A., Raker, J. W. Ann. 3. Sandeman, T. F. Lancet, 1965, i, 345.
Surg. 1965, 162, 15.
603 surgeons do not see enough cases) that a clinical trial is the only way to solve this controlled properly once and for all. The wide variation in published problem survival figures of series treated at different institutions makes comparison impossible, and the pitfalls of changing surgical technique make non-contemporaneous comparisons unreliable. My contention is not that the figures in such published series are wrong, that the operation should be condemned, and that therapeutic nihilism is the only course open-it is merely that the basis for the arguments for elective dissection are never presented in a form which can be usefully examined. The theory is indisputable, but the practice in my experience 3is less than satisfactory. It follows that there are other factors, influencing the results, which we already know. The adequacy of the surgery performed may be one, but unfortunately the dicta appearing in the medical journals are seldom accompanied-as your leader was-by a warning that only the experienced should attempt the difficult. In passing I would add to your otherwise excellent resume of the management of early malignant melanoma the observation that clinical judgment in a difficult case seems to be superior to frozen-section diagnosis. If clinical doubt exists it is better to remove the whole lesion, with small margins where possible, and await a more reliable paraffin-section report before subjecting the patient to a mutilating procedure. So long as excision is complete the ominous consequences of incisional biopsy are avoided.
size
(individual
Peter MacCallum Clinic, Melbourne.
T. F. SANDEMAN.
UNSATISFACTORY INFUSIONS OF SODIUM BICARBONATE SiR,łThe difficulty of producing satisfactory molar solutions of sodium bicarbonate (8-4%), about which Mr. Daniels wrote last week, has previously been reportedand to overcome the difficulty it was suggested that 0-01% of sodium edetate should be added to the solution. The deposit is probably due to the extraction of magnesium or calcium ions from the glass of the bottle, and some batches of bottles may cause greater difficulty than others. It has now been found desirable to increase the concentration of sodium edetate to 0-02%. The formula in current use in this hospital is now: sodium bicarbonate 8-4 g., sodium edetate 0-02 g., water for injection to 100 ml. The injection is prepared by the method described in the British Pharmacopaeia and is given a three-months expiry date. Pharmaceutical Department,
Royal Free Hospital, London, W.C.1.
J. W. HADGRAFT.
TREATMENT OF STATUS ASTHMATICUS states the physician’s case on status asthmaticus with his usual cogency. The decision to start intermittent positive-pressure ventilation (I.P.P.v.) demands, firstly, an estimate of the degree of respiratory and metabolic failure. This is a laboratory procedure about which there can be little argument. Secondly, a clinical assessment has to be made of the likelihood that the patient will survive without " last-resort " treatment. This assessment will be influenced by the experience of the attendant. A surgeon, presented with mucous plugs, will want to pull them out. An anaesthetist will not be content until the
mostly run by anaesthetists. In most cases I doubt if much harm is done. But there seems less to be gained from argument, in your columns or elsewhere, than from close accord, in a respiratory unit, between a physician and an anaesthetist whose minds are not closed to the possibility that each may are
have
something to contribute. Finally I wish strongly to endorse Dr. Grant’s central pointthe prompt and energetic medical treatment of all patients who develop an asthmatic attack lasting more than 6 hours. Acute Respiratory Unit, Auckland Hospital Board, Auckland, New Zealand.
E. A. HARRIS.
MEDIASTINAL AND RETROPERITONEAL FIBROSIS SIR,-In our article (Jan. 8) we mentioned that the combination of mediastinal and retroperitoneal lesions may be commoner than is believed. Ironically we have been proved correct by several of our correspondents who have drawn our attention to some cases inexcusably overlooked, 5 to others concealed by a noncommittal title, 23to an unpublished case,9and to another awaiting histological confirmation.lO It will make an amende honorable and assist future reviewers if we extract the data relevant to our article. Of the new total of 10 cases of combined lesions listed below, 6 are fairly definite, 1357 8 2 are probable, 2and 2 possible. 6 10 They are listed in the order in which they were published, and it should be noticed that the case of Partington,4published in February, 1961, is the same as that described by Inkley and Abbott in December, 1961, and referred to in our article. We have no clinical data on case 10, but of the other 9 only 1, atypical also in other respects, was female.Ages ranged from 25 to 64, the average being 45-6 years at the time of 7 necropsy, or when the diagnosis was established by surgery. 6 In 1 case the retroperitoneal lesion was a chance discovery at necropsy.1 In 4 the mediastinal lesion was a symptomless finding at necropsy 2 39 or on X-ray.sIn the other 4 the patient had symptoms referable to both mediastinum and retroperitoneum, appearing in that order in 3 4 7and in the reverse order in 1.55 We must withdraw the claim that our case was the first in which both lesions were diagnosed in life, for it was anticipated by Cameron et al. and Ardagh and Blake. In both of these cases, incidentally, the patient had a similar fibrotic lesion in one testis and epididymis. The case of Cameron et al. is unique in that the two lesions were anatomically continuous. A. D. MORGAN Department of Morbid Anatomy, Westminster School of Medicine, LAVINIA W. LOUGHRIDGE University of London, R. Y. CALNE. S.W.1. London,
SIR,-Dr. Grant (Feb. 12)
airway is
"
secured " and the patient pink, quiet, and preferably unconscious. A physician, with experience of seriously ill asthmatics who have recovered, will be more conservative, and may sometimes wait too long. The availability of an acute respiratory unit is bound to influence a general physician who has a worrying case on his hands. Once a patient is admitted to such a unit, the odds will usually be on earlier rather than later i.P.P.v., since these units 4.
Sandeman, T. F. Med. J. Aust. 1965, i, 42. 5. Hadgraft, J. W., Hewer, B. Pharm. J. 1964, 192, 544.
MATERNAL HYPERVENTILATION AND THE FŒTUS SIR,-Dr. Crawford (Feb. 19) emphasises the difficulty of using postpartum information for evaluation of intrapartum events, particularly when the mothers are exposed to spinal anxsthesia with episodes of hypotension and to vasopressor drugs as well as labour and delivery before the measurements are made. It may also be worth pointing out that the error in the determination of oxygen saturation with the method used by Dr. Crawford is so large that actual relations may be obscured. Tubbs, O. S. Thorax, 1946, 1, 247. Reed, W. G., Stinely, R. W. New Engl. J. Med. 1959, 261, 320. Riches, E. Jl R. Coll. Surg. Edinb. 1959, 5, 22. Partington, P. F. Am. J. Surg. 1961, 101, 239. Cameron, D. G., Boyle, S. T. I., Mathews, W. H. Can. med. Ass. J. 1961, 85, 227. 6. Benfield, J. R., Harrison, R. W., Moulder, P. V., Lyon, E. S., Graff, P. W. J. Am. med. Ass. 1962, 182, 579. 7. Ardagh, J. W., Blake, G. B. N.Z. med. J. 1964, 63, 362. 8. Morgan, A. D., Loughridge, L. W., Calne, R. Y. Lancet, Jan. 8, 1966, p. 67. 9. van Rossum, W. Personal communication. 10. McManus, J. Personal communication. 1. 2. 3. 4. 5.
J.
SIR,-In reply to the comments of Dr. Court Brown and colleagues on our report of the infant with " antimongolism ", we certainly do endorse the opinion that family his
studies are necessary. In this regard, our error was one of omission rather than that of commission, since chromosome studies had been performed on both parents, and their karyotypes were apparently normal. Since we do feel strongly about the need for the investigation of the parents of children with chromosomal abnormalities, we are now routinely investigating all the parents in the younger age-group who have had children with Down’s syndrome and other chromosomal aberrations. University of Louisville School of Medicine, Louisville, Kentucky, U.S.A.
SBRUM-VITAMIN-B12
LEVELS AND RECOVERY OF ADDED
VITAMIN-B12
IN
10 PATIENTS RECEIVING CHLORPROMAZINE
doses of chlorpromazine for several weeks before the sera were collected. We also added 100 pg. per ml. of vitamin-B12 to 6 of the sera, and 200 pg. per ml. to 3 of the sera, in order to determine whether the vitamin could be recovered in the assay. The results, summarised in the accompanying table, show that the serum-vitamin-B is levels were normal in all the patients, and that between 75% and 125% of the vitamin-Bl2 added to the sera was recovered. We have obtained a similar range of recovery of vitamin-B12 added to normal sera. In another experiment we observed that the addition of chlorpromazine to normal serum (1 mg. per ml.) did not affect the result of the vitamin-B12 assay. We can conclude from these results that chlorpromazine does not suppress the growth of L. leichmanii. JOHN FORSHAW Sefton General Hospital, LILIAN HARWOOD. Liverpool, 15.
MALIGNANT MELANOMA OF THE SKIN SIR,-While there is much in your leaderwith which I agree, I must take you to task on such a dogmatic statement as: Doubt can no longer exist that local excision of a malignant melanoma should be followed by prophylactic dissection of the regional nodes." Prophylactic is a poor term to use, since the operation does nothing to prevent disease. In some cases it removes subclinical deposits, but whether this adds to the comfort or survival of the individual patient is still not clearly settled. The principal article2 cited in support of your contention suffers, as do most if not all series of any size, in being neither controlled nor presented in a form which can be compared with similar series which are not electively treated. The presentation of results according to the pathological report can distort the figures, as I have shown.3 In addition, Mundth et al. estimated survival from the time of onset of diseasesurely a less than satisfactory index, depending as it does on "
LEONARD E. REISMAN.
"
SERUM-VITAMIN-B12 AND CHLORPROMAZINE SIR,-We have read with interest the article by Dr. Herbert and his colleagues6 in which they show that low Euglena gracilis serum-vitamin-B12 levels in patients receiving chlorpromazine therapy are an artefact. It should be pointed out, however, that their coated-charcoal assay, which was not affected by chlorpromazine, is an expensive method. In their
"
report of this method Herbert and his colleagues ’7 describe the use of 57Co-vitamin-B12 with a specific activity of 11 -.C per {l.g.; the approximate cost of this radioactive isotope would be C40 for the first serum-assay in each batch, and E20 for memory, and not record. Mundth et al. presented, not true each other serum-assay.8 Later (in 1965) Herbert 9 has stated ten-year survival figures, but those from patients who were that the 57Co-vitamin-B12 may have a specific activity as low followed up for between five and ten years. Over a quarter of as 1 jjt.C per {l.g., but he recommends 4 {iC per {ig. as the best cases were not used in their calculations; they died of specific activity to use. But, even if 5’Co-vitamin-Bl, with a their other (unstated) or were lost to follow-up. One of their specific activity of 1 {l.C per {l.g. were used, the cost of the tables causes is arithmetically incorrect on cross-checking, and the radioactive isotope would be roughly E4 for the first serumstandard errors are in many cases so high and the total numbers assay in a bath, and E2 for each other assay. so low that few firm conclusions should be drawn. Thus their In view of the fairly low cost of the Lactobacillus leichmanii " prophylactically " dissected positive-node group totals 18 serum-vitamin-B12 assay we considered that it was important cases, of which 5 were at some stage excluded from the to determine whether the results obtained with this method calculation. were affected by chlorpromazine therapy. We have therefore To cite only the percentage results from such reports lends the levels the L. leichmanii assayed by serum-vitamin-B12 a spurious air of statistical significance. To compare the method in 10 psychiatric patients on chlorpromazine therapy. of and positive on survivals those whose nodes were negative With one exception (no. 8) the patients had been taking large elective with those who eventually or initially required operation 3. Potter, E. L. Pathology of the Fetus and the Infant; p. 430. Chicago, 1961. dissection for clinically and histologically positive nodes invites 4. Macgregor, A. R. Pathology of Infancy and Childhood; p. 214. Edinburgh, 1960. the question: " What happened to those who had no elective 5. Passarge, E., Sutherland, J. M. Am. J. Dis. Child. 1965, 109, 80. " treatment and did not require dissection ? 6. Herbert, V., Gottlieb, C. W., Altschule, M. D. Lancet, 1965, ii, 1052. 7. Lau, K.-S., Gottlieb, C., Wasserman, L. R., Herbert, V. Blood, 1965, It seems to be impossible to persuade surgical centres of any 202. 8.
26, Catalogue of Radio-active products, Radiochemical Centre, Amersham, 1965-66; p. 75.
9.
Herbert, V. Personal communication.
1. Lancet, 1965, ii, 1171. 2. Mundth, E. D., Guralnick, E. A., Raker, J. W. Ann. 3. Sandeman, T. F. Lancet, 1965, i, 345.
Surg. 1965, 162, 15.
603 surgeons do not see enough cases) that a clinical trial is the only way to solve this controlled properly once and for all. The wide variation in published problem survival figures of series treated at different institutions makes comparison impossible, and the pitfalls of changing surgical technique make non-contemporaneous comparisons unreliable. My contention is not that the figures in such published series are wrong, that the operation should be condemned, and that therapeutic nihilism is the only course open-it is merely that the basis for the arguments for elective dissection are never presented in a form which can be usefully examined. The theory is indisputable, but the practice in my experience 3is less than satisfactory. It follows that there are other factors, influencing the results, which we already know. The adequacy of the surgery performed may be one, but unfortunately the dicta appearing in the medical journals are seldom accompanied-as your leader was-by a warning that only the experienced should attempt the difficult. In passing I would add to your otherwise excellent resume of the management of early malignant melanoma the observation that clinical judgment in a difficult case seems to be superior to frozen-section diagnosis. If clinical doubt exists it is better to remove the whole lesion, with small margins where possible, and await a more reliable paraffin-section report before subjecting the patient to a mutilating procedure. So long as excision is complete the ominous consequences of incisional biopsy are avoided.
size
(individual
Peter MacCallum Clinic, Melbourne.
T. F. SANDEMAN.
UNSATISFACTORY INFUSIONS OF SODIUM BICARBONATE SiR,łThe difficulty of producing satisfactory molar solutions of sodium bicarbonate (8-4%), about which Mr. Daniels wrote last week, has previously been reportedand to overcome the difficulty it was suggested that 0-01% of sodium edetate should be added to the solution. The deposit is probably due to the extraction of magnesium or calcium ions from the glass of the bottle, and some batches of bottles may cause greater difficulty than others. It has now been found desirable to increase the concentration of sodium edetate to 0-02%. The formula in current use in this hospital is now: sodium bicarbonate 8-4 g., sodium edetate 0-02 g., water for injection to 100 ml. The injection is prepared by the method described in the British Pharmacopaeia and is given a three-months expiry date. Pharmaceutical Department,
Royal Free Hospital, London, W.C.1.
J. W. HADGRAFT.
TREATMENT OF STATUS ASTHMATICUS states the physician’s case on status asthmaticus with his usual cogency. The decision to start intermittent positive-pressure ventilation (I.P.P.v.) demands, firstly, an estimate of the degree of respiratory and metabolic failure. This is a laboratory procedure about which there can be little argument. Secondly, a clinical assessment has to be made of the likelihood that the patient will survive without " last-resort " treatment. This assessment will be influenced by the experience of the attendant. A surgeon, presented with mucous plugs, will want to pull them out. An anaesthetist will not be content until the
mostly run by anaesthetists. In most cases I doubt if much harm is done. But there seems less to be gained from argument, in your columns or elsewhere, than from close accord, in a respiratory unit, between a physician and an anaesthetist whose minds are not closed to the possibility that each may are
have
something to contribute. Finally I wish strongly to endorse Dr. Grant’s central pointthe prompt and energetic medical treatment of all patients who develop an asthmatic attack lasting more than 6 hours. Acute Respiratory Unit, Auckland Hospital Board, Auckland, New Zealand.
E. A. HARRIS.
MEDIASTINAL AND RETROPERITONEAL FIBROSIS SIR,-In our article (Jan. 8) we mentioned that the combination of mediastinal and retroperitoneal lesions may be commoner than is believed. Ironically we have been proved correct by several of our correspondents who have drawn our attention to some cases inexcusably overlooked, 5 to others concealed by a noncommittal title, 23to an unpublished case,9and to another awaiting histological confirmation.lO It will make an amende honorable and assist future reviewers if we extract the data relevant to our article. Of the new total of 10 cases of combined lesions listed below, 6 are fairly definite, 1357 8 2 are probable, 2and 2 possible. 6 10 They are listed in the order in which they were published, and it should be noticed that the case of Partington,4published in February, 1961, is the same as that described by Inkley and Abbott in December, 1961, and referred to in our article. We have no clinical data on case 10, but of the other 9 only 1, atypical also in other respects, was female.Ages ranged from 25 to 64, the average being 45-6 years at the time of 7 necropsy, or when the diagnosis was established by surgery. 6 In 1 case the retroperitoneal lesion was a chance discovery at necropsy.1 In 4 the mediastinal lesion was a symptomless finding at necropsy 2 39 or on X-ray.sIn the other 4 the patient had symptoms referable to both mediastinum and retroperitoneum, appearing in that order in 3 4 7and in the reverse order in 1.55 We must withdraw the claim that our case was the first in which both lesions were diagnosed in life, for it was anticipated by Cameron et al. and Ardagh and Blake. In both of these cases, incidentally, the patient had a similar fibrotic lesion in one testis and epididymis. The case of Cameron et al. is unique in that the two lesions were anatomically continuous. A. D. MORGAN Department of Morbid Anatomy, Westminster School of Medicine, LAVINIA W. LOUGHRIDGE University of London, R. Y. CALNE. S.W.1. London,
SIR,-Dr. Grant (Feb. 12)
airway is
"
secured " and the patient pink, quiet, and preferably unconscious. A physician, with experience of seriously ill asthmatics who have recovered, will be more conservative, and may sometimes wait too long. The availability of an acute respiratory unit is bound to influence a general physician who has a worrying case on his hands. Once a patient is admitted to such a unit, the odds will usually be on earlier rather than later i.P.P.v., since these units 4.
Sandeman, T. F. Med. J. Aust. 1965, i, 42. 5. Hadgraft, J. W., Hewer, B. Pharm. J. 1964, 192, 544.
MATERNAL HYPERVENTILATION AND THE FŒTUS SIR,-Dr. Crawford (Feb. 19) emphasises the difficulty of using postpartum information for evaluation of intrapartum events, particularly when the mothers are exposed to spinal anxsthesia with episodes of hypotension and to vasopressor drugs as well as labour and delivery before the measurements are made. It may also be worth pointing out that the error in the determination of oxygen saturation with the method used by Dr. Crawford is so large that actual relations may be obscured. Tubbs, O. S. Thorax, 1946, 1, 247. Reed, W. G., Stinely, R. W. New Engl. J. Med. 1959, 261, 320. Riches, E. Jl R. Coll. Surg. Edinb. 1959, 5, 22. Partington, P. F. Am. J. Surg. 1961, 101, 239. Cameron, D. G., Boyle, S. T. I., Mathews, W. H. Can. med. Ass. J. 1961, 85, 227. 6. Benfield, J. R., Harrison, R. W., Moulder, P. V., Lyon, E. S., Graff, P. W. J. Am. med. Ass. 1962, 182, 579. 7. Ardagh, J. W., Blake, G. B. N.Z. med. J. 1964, 63, 362. 8. Morgan, A. D., Loughridge, L. W., Calne, R. Y. Lancet, Jan. 8, 1966, p. 67. 9. van Rossum, W. Personal communication. 10. McManus, J. Personal communication. 1. 2. 3. 4. 5.