- Email: [email protected]
TRIUMPHS FOR CHEMISTS
710
pulmonary hypertension.
ENTICKNAP
28
found that
local hospital. They know that the operation will always be performed there in technically satisfactory circumpreceded by capillary dilatation, and he suggested stances, though the attendance may be a considerable that the organic arteriolar changes depended on inconvenience to the patient and the operation a pulmonary arterial, rather than venous, hypertension. nuisance to the casualty officer. But absence of hyalinisation (which characterises the In the valuable article which we publish this week, Dr. J. H. HUNT develops a principle which, if applied lesions arterial systemic produced by hypertension) in all -his cases led ENTICKNAP to postulate that in thelarger hospitals, might resolve the difficulty pulmonary and systemic arterioles might differ funda- to the advantage of both hospital and practitioner. mentally. In 4 of his cases thrombi were found in the It should not be impossible to establish, at hospitals arterioles, and these thrombi might have accounted with large casualty departments, a minor-operations for the sclerosis. Possibly repeated thromboses or theatre where visiting general practitioners could do thrombo-embolism may account partly for the their own minor surgery. Such a department could arteriolar changes, but - conclusive proof is lacking. be efficiently staffed and equipped, and the services Rheumatic arteritis in the main pulmonary arteries, of an anaesthetist should be easily forthcoming. and occasionally in the smaller branches, has been Local circumstances would determine whether all reported,29 30 but this is unlikely to play any impor- the work of a department such as this would be done tant part in bringing about arteriolar sclerosis or by doctors on their own patients,’ or whether, as Dr. HUNT suggests, a general-practitioner specialist" pulmonary hypertension. 20 31 should be appointed on a sessional basis. Either way, the casualty officer would be relieved of much Scalpel in the Surgery ? non-casualty work which he may find hard to fit THE amount of minor surgery met with in general into a programme not designed for it. practice may vary a little, according to the type of There are all too few links between the large hospractice and the kind of industries in the locality ; pital and the general practices that feed it, and if but the attitude of the practitioner to its performance this* one were to be forged it might do great good. varies very widely. To some it is a skill to be developed It is in casualty that the young hospital resident and increased, while to others it is a time-consuming sees what he takes to be examples of the inefficiency hindrance to the proper work of the day. and ineptitude of the family doctor. It would be Perhaps not very long ago the practitioner of better for him if he were taught his minor surgery today was himself a final-year student or a house- by a competent general practitioner who could give man taking his part in the busy routine of casualty him an understanding of the background to whatand surgical outpatients, gaining experience and ever surgical procedure is undertaken. judgment as well as dexterity in the lesser surgical procedures left to him by colleagues whose eyes were Annotations The on higher planes of surgical achievement. sebaceous cyst, the circumcision, the localised abscess TRIUMPHS FOR CHEMISTS -these opportunities are met with often enough in Two notable of chemical research have been general practice to encourage any practitioner who announced that pieces are of direct interest to medical men. wants to maintain his skill and to gain the added The first of these (as already noted briefly in these satisfaction of seeing his own patient through yet is the elucidation of the structure of the columns’) one more clinical adventure. In the country-town molecule of vitamin B12’ or cyanocobalamin as it is practice (where there is an operating-theatre at the officially named. Isolated and introduced to medicine cottage hospital), in the few prototype health centres, seven years ago, vitamin B12 is exceptional among bioand in a few group-practice units, there may be logical substances of importance in human nutrition " minor ops " theatres equipped to a standard of because it contains cobalt. It is now well known that essential for the proper development of efficiency that the single-handed practitioner cannot the vitamin isand the commonest disease in this country erythroblasts, achieve. In urban practice, however, where group with which connected is is pernicious anaemia. In it practices are less common, practitioners will under- this disease the vitamin is not absorbed, and the ansemia. take their own minor operations less often. As the is relieved by administering the vitamin parenterally items of service making up a day can usually be in very small doses, measured in microgrammes. rearranged to enable a desired object to be achieved, The elucidation of the chemical nature of vitamin B,2 we must presume that it is not simply the lack of has resulted from a combination of crystallographic time that discourages such work, but a combination work at Oxford, calculation at Los Angeles, and chemical studies at Cambridge and the Glaxo Laboratories at of factors including inadequacy of premises (a satisGreenford, Middlesex. The crystallographic part was is room not examination a factory necessarily good carried out by Dorothy Hodgkin and her colleagues. theatre), difficulty in getting the help of an anoes- To the uninitiated some of the that illustrate
arteriolar sclerosis in the
lungs
was
not
"
thetist, absence, of
recovery room, and often lack of the trained nursing help which makes the maintenance of strict surgical sterility practicable. For such reasons many family doctors, though well able to do their own minor surgery competently, refer their patients to the casualty department of their 28. 29.
Enticknap, J.
a
B. Ibid, 1953, 6, 84. Kugel, M. A., Epstein, E. J. Arch. Path. (Lab. Med.) 1928, 6, 247. 30. Gross, L. Amer. J. Path. 1935, 11, 631. 31. Friedberg, C. K. Diseases of the Heart. Philadelphia, 1949.
diagrams
their paper look like maps of London’s Underground, and others appear to belong to, space fiction. - We are not surprised to learn that Dr. Hodgkin and her colleagues at Oxford had to call in Californian cybernetic assistance in the shape of SWAC (National Bureau of Standards western automatic computer) to help them with their calculations. The formula they eventually proposed was complex and represents a considerable achievement for 1. Lancet, Aug. 20, 1955, p. 402. 2. Hodgkin, D. C., Pickworth, J., Robertson, J. H., Trueblood, K. N., Prosen, R. J. Nature, Lond. 1955, 176, 325.
711 " To be able to write down a chemical very largely from purely crystallographic evidence on the arrangement of atoms in space-and the chemical structure of a quite formidably large molecule at that-is," they say, " for any crystallographer something of a dream-like situation." The crystallographic data by themselves left a number of points in doubt, and these have been tested and largely resolved by the workers at Cambridge and Greenford,3 An interesting who used regular chemical methods. feature of the molecule of vitamin B12 (C63Hgo014N14PCO) is the cyclic grouping round the cobalt atom, which is that present in the porphyrins. The second chemical triumph is the determination of the structure of the insulin molecule. Insulin proved a much harder problem than vitamin Bm and ten years have elapsed since Sanger and his colleagues at Cambridge published their first paper on this subject. The details now described by Sanger et awl. show that, compared to vitamin B12, insulin has an enormous molecule with the empirical formula C254H377075N 65S6’ giving a molecular weight of 5733-5. The structure of the molecule consists of two parallel straight polypeptide chains linked by sulphur bridges that are parts of cystine residues. These two polypeptide chains are not, as might be expected, equal in length ; the upper chain contains 21 units and the lower chain 30 units (counting each cystine residue as 2 cysteine units) ; so the insulin molecule must be askew in some manner, possibly coiled. Analysis of the amino-acids present in the molecule showed that leucine occurs most frequently at six times, valine five times, glutamic acid, glycine, and tyrosine four times, aspargine, alanine, cystine, glutamine, phenylalanine, and serine are represented three times, histidine twice, and arginine, lysine, proline, and threonine only once. Notable absentees are methionine and tryptophane. The exact arrangement of these aminoacids in the two parallel chains has been worked out in detail by Sanger and his colleagues-a very striking piece of chemical detective work. The Cambridge group have also shown5 that there are small differences in the composition of the polypeptide chains of the insulins of different species ; cattle, pig, and sheep insulins differ from each other in this way. The elucidation of the structure of insulin and vitamin B12 may point the way to their eventual synthesis. on chemical knowThe supply of cortisone has ledge of the structure of the drug and its partial synthesis. But for both vitamin B12 and insulin we have efficient biological sources, the use of which has been brought to Moreover these substances a high degree of perfection. A diabetic are produced remarkably inexpensively. patient on 40 units of insulin zinc suspension daily uses about 7 pennyworth of insulin ; while for the patient with pernicious anaemia on 100 (j(.g. vitamin B12 weekly the cost is about 10d. (the streptomyces that produces the vitamin is a notably efficient organic chemist). The and posterior-pituitary hormones, oxytocin vasopressin, and at least one of the anterior-pituitary hormones have known chemical structures and have already been synthesised by American workers, but the methods of synthesis are not at present suitable for large-scale production. Yet even if knowledge of structure does not affect the supply of material for treatment, it is very important. We hope that fundamental information of this sort will help us to understand the mode of action of insulin, vitamin B1, and the others ; it may lead to better treatment and even aid prevention in the long run. Doctors will watch with unsimulated interest the results of the efforts of their chemical colleagues, even though they may not follow the technical details.
crystallography.
structure
depended
3. 4.
Bonnett, R., Cannon,
J.
R., Johnson, A. W., Sutherland, I.,
Todd, A. R., Smith, E. L. Ibid, p. 328. Ryle, A. P., Sanger, F., Smith, L. F., Kitai, 1955, 60, 541.
5. Brown, H., Sanger, F., Kitai,
R. Ibid, p. 556.
R.
Biochem. J.
SYNTHETIC ARTERIAL GRAFTS
forty years arterial surgery stood where this century’s early pioneers had left it. Only by local repair was it possible to reconstruct a major artery. Grafting with a segment of vein, though occasionally successful, never became a standard method of bridging the longer defects. In 1949 Gross and his colleagues1 described the clinical application of Carrel’s method of homografting with the stored arteries of another individual. FOR
Since then surgeons all
the world have followed this to and including the aortic arch can now be excised and the artery reconstructed. Such arterial segments are usually dead when implanted, and they do not retain their original structure for long afterwards. Within a few weeks only extracellular material (mainly the elastic layers) remains. The main virtue of the arterial homograft, apart from its smooth lining and elasticity, seems to lie in its negative fe,i,tures-its inertness and the mildness of the reaction that it evokes, confined to a slow, healing incorporation which secures its function as a major blood-vessel. Human arterial grafts are scarce. Even with permanent storage, such as is now possible with deepfreezing2 and freeze-drying,3 the essential difficulty of procuring the grafts remains. Other forms of prosthesis have been tried. Intubation of the arterial defect by rigid protheses of metal, glass, or plastic nearly always leads to haemorrhage or thrombosis, though Hufnagel and his colleagues4 have shown that in the thoracic aorta of man and the dog a polishedPerspex ’ tube or ballvalve will usually remain patent if fixed by a multi-’ pointed nylon ring at either end. Below this level, and particularly where the soft tissues are mobile, all methods involving rigid tubes may be expected to fail. A much more promising method was introduced by Voorhees et awl. They fashioned tubes of a plastic cloth,Vinyon N,’ and sutured these into the dog’s abdominal aorta. The results encouraged them to use the same method in patients urgently needing operation, and in 1954 they reported good results after grafting with this material in 18 patients, mostly with abdominal aneurysms.6 The technique of inserting cloth tubes is much the same as that of homografting. When the arterial clamps are released blood leaks between the interstices of the fabric. The amount of bleeding depends on the material used, its weave, and its water-repellancy. Vinyon N is less satisfactory in this respect than finer fabrics such as ’Orlon,’’Dacron’ (’Terylene’), and nylon. It generally needs to be pre-clotted " by preliminary exposure to whole blood, either in vitro or by prolonging the interval between removal of the distal clamp and removal -of the proximal clamp. A liberal amount of enmeshed fibrin is helpful in that it provides a medium for the migration of fibroblasts, which organise the prosthesis into a living fibrous tube with a durable cloth reinforcement. This would seem to be an excellent substitute for a homograft : in fact it may prove in some ways even better, for homografts may have a limited life. Degenerative changes have already been reported in early dog preparations,7 but there are so far no reports of late failure in cases grafted with suitable material by established methods. Arterial grafts have now been applied in several hundred cases, some as long ago as 1948. At St. Mary’s Hospital, London, alone over 100 such grafts have now been applied, 40 of them to the aorta. Most of these were over
lead, and major arterial lesions up
‘
"
1. Gross, R. E., Bill, A. H., Peirce, E. C. 1949, 88, 689. 2. Eastcott, H. H. G., Hufnagel, C. A.
Surg. Gynec. Obstet.
Surg. Forum, 1950, p. 269. P. Ann. L. 3. Marrangoni, A. G., Cecchini, Surg. 1951, 134, 977. 4. Hufnagel, C. A., Rabil, P., Harvey, W. P., McDermott, 673. T. F. Surgery, 1954, 35, 5. Voorhees, A. B., Jaretski, A., Blakemore, A. H. Ann. Surg. 1952, 135, 332. 6. Blakemore, A. H., Voorhees, A. B. Ibid, 1954, 140, 324. 7. Coleman, C. C. jun., Deterling, R. A. jun., Parshley, M. S. Surgery, 1955, 37, 64.
pulmonary hypertension.
ENTICKNAP
28
found that
local hospital. They know that the operation will always be performed there in technically satisfactory circumpreceded by capillary dilatation, and he suggested stances, though the attendance may be a considerable that the organic arteriolar changes depended on inconvenience to the patient and the operation a pulmonary arterial, rather than venous, hypertension. nuisance to the casualty officer. But absence of hyalinisation (which characterises the In the valuable article which we publish this week, Dr. J. H. HUNT develops a principle which, if applied lesions arterial systemic produced by hypertension) in all -his cases led ENTICKNAP to postulate that in thelarger hospitals, might resolve the difficulty pulmonary and systemic arterioles might differ funda- to the advantage of both hospital and practitioner. mentally. In 4 of his cases thrombi were found in the It should not be impossible to establish, at hospitals arterioles, and these thrombi might have accounted with large casualty departments, a minor-operations for the sclerosis. Possibly repeated thromboses or theatre where visiting general practitioners could do thrombo-embolism may account partly for the their own minor surgery. Such a department could arteriolar changes, but - conclusive proof is lacking. be efficiently staffed and equipped, and the services Rheumatic arteritis in the main pulmonary arteries, of an anaesthetist should be easily forthcoming. and occasionally in the smaller branches, has been Local circumstances would determine whether all reported,29 30 but this is unlikely to play any impor- the work of a department such as this would be done tant part in bringing about arteriolar sclerosis or by doctors on their own patients,’ or whether, as Dr. HUNT suggests, a general-practitioner specialist" pulmonary hypertension. 20 31 should be appointed on a sessional basis. Either way, the casualty officer would be relieved of much Scalpel in the Surgery ? non-casualty work which he may find hard to fit THE amount of minor surgery met with in general into a programme not designed for it. practice may vary a little, according to the type of There are all too few links between the large hospractice and the kind of industries in the locality ; pital and the general practices that feed it, and if but the attitude of the practitioner to its performance this* one were to be forged it might do great good. varies very widely. To some it is a skill to be developed It is in casualty that the young hospital resident and increased, while to others it is a time-consuming sees what he takes to be examples of the inefficiency hindrance to the proper work of the day. and ineptitude of the family doctor. It would be Perhaps not very long ago the practitioner of better for him if he were taught his minor surgery today was himself a final-year student or a house- by a competent general practitioner who could give man taking his part in the busy routine of casualty him an understanding of the background to whatand surgical outpatients, gaining experience and ever surgical procedure is undertaken. judgment as well as dexterity in the lesser surgical procedures left to him by colleagues whose eyes were Annotations The on higher planes of surgical achievement. sebaceous cyst, the circumcision, the localised abscess TRIUMPHS FOR CHEMISTS -these opportunities are met with often enough in Two notable of chemical research have been general practice to encourage any practitioner who announced that pieces are of direct interest to medical men. wants to maintain his skill and to gain the added The first of these (as already noted briefly in these satisfaction of seeing his own patient through yet is the elucidation of the structure of the columns’) one more clinical adventure. In the country-town molecule of vitamin B12’ or cyanocobalamin as it is practice (where there is an operating-theatre at the officially named. Isolated and introduced to medicine cottage hospital), in the few prototype health centres, seven years ago, vitamin B12 is exceptional among bioand in a few group-practice units, there may be logical substances of importance in human nutrition " minor ops " theatres equipped to a standard of because it contains cobalt. It is now well known that essential for the proper development of efficiency that the single-handed practitioner cannot the vitamin isand the commonest disease in this country erythroblasts, achieve. In urban practice, however, where group with which connected is is pernicious anaemia. In it practices are less common, practitioners will under- this disease the vitamin is not absorbed, and the ansemia. take their own minor operations less often. As the is relieved by administering the vitamin parenterally items of service making up a day can usually be in very small doses, measured in microgrammes. rearranged to enable a desired object to be achieved, The elucidation of the chemical nature of vitamin B,2 we must presume that it is not simply the lack of has resulted from a combination of crystallographic time that discourages such work, but a combination work at Oxford, calculation at Los Angeles, and chemical studies at Cambridge and the Glaxo Laboratories at of factors including inadequacy of premises (a satisGreenford, Middlesex. The crystallographic part was is room not examination a factory necessarily good carried out by Dorothy Hodgkin and her colleagues. theatre), difficulty in getting the help of an anoes- To the uninitiated some of the that illustrate
arteriolar sclerosis in the
lungs
was
not
"
thetist, absence, of
recovery room, and often lack of the trained nursing help which makes the maintenance of strict surgical sterility practicable. For such reasons many family doctors, though well able to do their own minor surgery competently, refer their patients to the casualty department of their 28. 29.
Enticknap, J.
a
B. Ibid, 1953, 6, 84. Kugel, M. A., Epstein, E. J. Arch. Path. (Lab. Med.) 1928, 6, 247. 30. Gross, L. Amer. J. Path. 1935, 11, 631. 31. Friedberg, C. K. Diseases of the Heart. Philadelphia, 1949.
diagrams
their paper look like maps of London’s Underground, and others appear to belong to, space fiction. - We are not surprised to learn that Dr. Hodgkin and her colleagues at Oxford had to call in Californian cybernetic assistance in the shape of SWAC (National Bureau of Standards western automatic computer) to help them with their calculations. The formula they eventually proposed was complex and represents a considerable achievement for 1. Lancet, Aug. 20, 1955, p. 402. 2. Hodgkin, D. C., Pickworth, J., Robertson, J. H., Trueblood, K. N., Prosen, R. J. Nature, Lond. 1955, 176, 325.
711 " To be able to write down a chemical very largely from purely crystallographic evidence on the arrangement of atoms in space-and the chemical structure of a quite formidably large molecule at that-is," they say, " for any crystallographer something of a dream-like situation." The crystallographic data by themselves left a number of points in doubt, and these have been tested and largely resolved by the workers at Cambridge and Greenford,3 An interesting who used regular chemical methods. feature of the molecule of vitamin B12 (C63Hgo014N14PCO) is the cyclic grouping round the cobalt atom, which is that present in the porphyrins. The second chemical triumph is the determination of the structure of the insulin molecule. Insulin proved a much harder problem than vitamin Bm and ten years have elapsed since Sanger and his colleagues at Cambridge published their first paper on this subject. The details now described by Sanger et awl. show that, compared to vitamin B12, insulin has an enormous molecule with the empirical formula C254H377075N 65S6’ giving a molecular weight of 5733-5. The structure of the molecule consists of two parallel straight polypeptide chains linked by sulphur bridges that are parts of cystine residues. These two polypeptide chains are not, as might be expected, equal in length ; the upper chain contains 21 units and the lower chain 30 units (counting each cystine residue as 2 cysteine units) ; so the insulin molecule must be askew in some manner, possibly coiled. Analysis of the amino-acids present in the molecule showed that leucine occurs most frequently at six times, valine five times, glutamic acid, glycine, and tyrosine four times, aspargine, alanine, cystine, glutamine, phenylalanine, and serine are represented three times, histidine twice, and arginine, lysine, proline, and threonine only once. Notable absentees are methionine and tryptophane. The exact arrangement of these aminoacids in the two parallel chains has been worked out in detail by Sanger and his colleagues-a very striking piece of chemical detective work. The Cambridge group have also shown5 that there are small differences in the composition of the polypeptide chains of the insulins of different species ; cattle, pig, and sheep insulins differ from each other in this way. The elucidation of the structure of insulin and vitamin B12 may point the way to their eventual synthesis. on chemical knowThe supply of cortisone has ledge of the structure of the drug and its partial synthesis. But for both vitamin B12 and insulin we have efficient biological sources, the use of which has been brought to Moreover these substances a high degree of perfection. A diabetic are produced remarkably inexpensively. patient on 40 units of insulin zinc suspension daily uses about 7 pennyworth of insulin ; while for the patient with pernicious anaemia on 100 (j(.g. vitamin B12 weekly the cost is about 10d. (the streptomyces that produces the vitamin is a notably efficient organic chemist). The and posterior-pituitary hormones, oxytocin vasopressin, and at least one of the anterior-pituitary hormones have known chemical structures and have already been synthesised by American workers, but the methods of synthesis are not at present suitable for large-scale production. Yet even if knowledge of structure does not affect the supply of material for treatment, it is very important. We hope that fundamental information of this sort will help us to understand the mode of action of insulin, vitamin B1, and the others ; it may lead to better treatment and even aid prevention in the long run. Doctors will watch with unsimulated interest the results of the efforts of their chemical colleagues, even though they may not follow the technical details.
crystallography.
structure
depended
3. 4.
Bonnett, R., Cannon,
J.
R., Johnson, A. W., Sutherland, I.,
Todd, A. R., Smith, E. L. Ibid, p. 328. Ryle, A. P., Sanger, F., Smith, L. F., Kitai, 1955, 60, 541.
5. Brown, H., Sanger, F., Kitai,
R. Ibid, p. 556.
R.
Biochem. J.
SYNTHETIC ARTERIAL GRAFTS
forty years arterial surgery stood where this century’s early pioneers had left it. Only by local repair was it possible to reconstruct a major artery. Grafting with a segment of vein, though occasionally successful, never became a standard method of bridging the longer defects. In 1949 Gross and his colleagues1 described the clinical application of Carrel’s method of homografting with the stored arteries of another individual. FOR
Since then surgeons all
the world have followed this to and including the aortic arch can now be excised and the artery reconstructed. Such arterial segments are usually dead when implanted, and they do not retain their original structure for long afterwards. Within a few weeks only extracellular material (mainly the elastic layers) remains. The main virtue of the arterial homograft, apart from its smooth lining and elasticity, seems to lie in its negative fe,i,tures-its inertness and the mildness of the reaction that it evokes, confined to a slow, healing incorporation which secures its function as a major blood-vessel. Human arterial grafts are scarce. Even with permanent storage, such as is now possible with deepfreezing2 and freeze-drying,3 the essential difficulty of procuring the grafts remains. Other forms of prosthesis have been tried. Intubation of the arterial defect by rigid protheses of metal, glass, or plastic nearly always leads to haemorrhage or thrombosis, though Hufnagel and his colleagues4 have shown that in the thoracic aorta of man and the dog a polishedPerspex ’ tube or ballvalve will usually remain patent if fixed by a multi-’ pointed nylon ring at either end. Below this level, and particularly where the soft tissues are mobile, all methods involving rigid tubes may be expected to fail. A much more promising method was introduced by Voorhees et awl. They fashioned tubes of a plastic cloth,Vinyon N,’ and sutured these into the dog’s abdominal aorta. The results encouraged them to use the same method in patients urgently needing operation, and in 1954 they reported good results after grafting with this material in 18 patients, mostly with abdominal aneurysms.6 The technique of inserting cloth tubes is much the same as that of homografting. When the arterial clamps are released blood leaks between the interstices of the fabric. The amount of bleeding depends on the material used, its weave, and its water-repellancy. Vinyon N is less satisfactory in this respect than finer fabrics such as ’Orlon,’’Dacron’ (’Terylene’), and nylon. It generally needs to be pre-clotted " by preliminary exposure to whole blood, either in vitro or by prolonging the interval between removal of the distal clamp and removal -of the proximal clamp. A liberal amount of enmeshed fibrin is helpful in that it provides a medium for the migration of fibroblasts, which organise the prosthesis into a living fibrous tube with a durable cloth reinforcement. This would seem to be an excellent substitute for a homograft : in fact it may prove in some ways even better, for homografts may have a limited life. Degenerative changes have already been reported in early dog preparations,7 but there are so far no reports of late failure in cases grafted with suitable material by established methods. Arterial grafts have now been applied in several hundred cases, some as long ago as 1948. At St. Mary’s Hospital, London, alone over 100 such grafts have now been applied, 40 of them to the aorta. Most of these were over
lead, and major arterial lesions up
‘
"
1. Gross, R. E., Bill, A. H., Peirce, E. C. 1949, 88, 689. 2. Eastcott, H. H. G., Hufnagel, C. A.
Surg. Gynec. Obstet.
Surg. Forum, 1950, p. 269. P. Ann. L. 3. Marrangoni, A. G., Cecchini, Surg. 1951, 134, 977. 4. Hufnagel, C. A., Rabil, P., Harvey, W. P., McDermott, 673. T. F. Surgery, 1954, 35, 5. Voorhees, A. B., Jaretski, A., Blakemore, A. H. Ann. Surg. 1952, 135, 332. 6. Blakemore, A. H., Voorhees, A. B. Ibid, 1954, 140, 324. 7. Coleman, C. C. jun., Deterling, R. A. jun., Parshley, M. S. Surgery, 1955, 37, 64.