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ORTHOPÆDIC JUDGMENT
552
Annotations POLIOMYELITIS: A NEW APPROACH IMMUNISATION against virus diseases has had its two great successes with smallpox and yellow fever, against each of which living " attenuated " virus is used. In contrast, immunisation with inactivated viruses against such diseases as influenza and mumps has been much With poliomyelitis, however, both less successful. types of approach have been followed. Morgan1 has shown that immunisation of monkeys by parenteral inoculation with inactivated poliomyelitis virus produces serum antibody in high titre and some resistance to challenge with virulent virus. There are, however, two serious obstacles to applying this experimental finding to man : first, poliomyelitis virus cannot be readily purified from the normal constituents of nervous tissue, which are known to produce allergic encephalitis ; and secondly, as in many fields, there is the difficulty of finding enough animals to produce enough virus for man’s demands. On the other hand, the use of a multiplying attenuated virus for immunisation in man is at least feasible. Howe and Bodian2 have infected chimpanzees by feeding them with poliomyelitis virus ; and Melnick and Horstmann3 have shown that such animals become intestinal carriers, excrete virus in their stools, develop serum antibody, and resist reinfection. In his Herter lectures Burnet4 said : "
The logical approach from the ecological angle toward prevention of poliomyelitis is either to find acceptable of ensuring a reasonable transfer of intestinal means infections between children in infancy or to devise some the
of effective immunisation. The technical difficulties a dead virus vaccine seem at the present to be insurmountable, and I feel confident that sooner or later it will become necessary to use living vaccines given by mouth in infancy, perhaps under cover of gamma globulin means
of
obtaining
passive protection." The way to experiments in human immunisation lay open; but who would have the courage to bell the cat ? Koprowski and his associates,5 in a most important paper, describe the results of feeding live poliomyelitis virus of low virulence to 20 volunteers. The virus which they used was prepared from the brain and spinal cord of cotton-rats infected with a rodent-adapted strain of poliomyelitis virus. In none of the 20 were signs or symptoms of illness noted, despite strict watch for any rise of temperature or evidence of gastro-intestinal or neurological disturbance. Most of the volunteers, however, became intestinal carriers of virus ; and all who were not initially immune developed antibodies in their blood to the homologous Lansing type viruses, but not to the heterologous Brunhilde type viruses which seem to be the commonest type isolated at present from cases of poliomyelitis. All interested in poliomyelitis will await further developments of this work with very great interest. But Koprowski and his colleagues are careful to point out that discussion of immunisation by oral administration of poliomyelitis virus is best deferred until this procedure is proved safe. Attenuated organisms of all three immunological types of poliomyelitis virus might be required ; and the brilliant work of Enders et al. in growing the virus in tissue cultures may help to furnish this. Koprowski et al. tell us in a footnote that for obvious reasons the age, sex, and physical status of each volunteer The reasons must be more obvious are not mentioned. to the authors than to the reader, who can only guess, Morgan, I. M. Amer. J. Hyg. 1948, 48, 394. Howe, H. A., Bodian, D. J. exp. Med. 1945, 81, 247. Melnick, J. L., Horstmann, D. M. Ibid, 1947, 85, 287. Burnet, F. M. Bull. Johns Hopk. Hosp. 1951, 88, 119. Koprowski, H., Jervis, G. A., Norton, T. W. Amer. J. Hyg 1952, 55, 108. 6. Enders, J. F., Weller, T. H., Robbins, F. C. Science, 1949 109, 85.
1. 2. 3. 4. 5.
from the methods used for feeding the virus, that the volunteers were very young and that the volunteering One of the reasons for the was done by their parents. richness of ,the English language is that the meaning of some words is continually changing. Such a word is " volunteer." We may yet read in a scientific journal that an experiment was carried out with twenty volunteer mice, and that twenty other mice volunteered as controls.
ORTHOPÆDIC JUDGMENT WHEREAS in many other branches of surgery the saving of life must be the paramount concern, the success of an orthopaedic operation is judged by the extent to which the patient is rid of his pain and relieved of his disability. It is this distinction, said Mr. Philip Wiles in his presidential address to the section of ortho. paedics of the Royal Society of Medicine on March 4, that lays upon the orthopaedic surgeon a special responsi. bility when he advises a patient to undergo an operation. The surgeon must be particularly confident that the patient will emerge an abler and more comfortable body than before ; that his improvement will justify the ordeal ; and that the risk of surgery is a reasonable one in the circumstances. The apparently irrational fears of the patient should be respected : it is too often disastrous to persuade an unwilling person to have an operation. Since it is our aim, said Mr. Wiles, to relieve symptoms, it is the sufferer who must finally weigh the risk and balance his apprehensions against the probable gain. Moreover, it is easy to say : " Come into hospital and I’ll put you right in no time " ; but what is the cost to a man and his familyg He may have been able to continue work despite, for example, a prolapsed intervertebral disc. How often, Mr. Wiles asked his audience, have you seen that same man six or twelve months after operation when he was still not back at his old work ? For the completely incapacitated the risk may be justified, but who shall judge in other circumstances! The right time for operation is when the patient knows the dangers and is willing, and indeed anxious, to face them. But Mr. Wiles thought that the hardest thing of all is to give a proper estimate of the benefit which may reasonably be expected from operation. There are so many variables : on the one hand, the personality of the patient, his threshold for pain, and his cooperation; on the other, his physical condition and the response of his tissues to the operation and the subsequent reablement. The answer is a guess, though it is a guess which becomes more and more accurate as the experience of the surgeon grows. Turning to the opportunities for the younger man, Mr. Wiles remarked that, while instruction in the actual techniques of orthopaedics is not hard to get, it is none too easy nowadays to acquire the essential basic training in general surgery. Rapid specialisation has changed the pattern and character of surgery in the last twenty or thirty years. " How is the surgeon in training to obtain a sufficiently varied experience now that the general surgical wards no longer contain a representative cross-section of surgical practice ?" he asked. And " how should the surgical beds of a teaching hospital be divided to give sufficient representation to the " specialties and yet maintain a proper balance Both questions could in part be answered, he thought, by giving the specialised surgeon a larger share in the teaching of basic surgery and by allotting him certain of the teaching beds now labelled " general surgery." Thus a student would spend, say, three months of a six months’ surgical appointment with a genito-urinary, an orthopaedic, or a rectal surgeon, who would use his special cases to illustrate surgical principles. The number of men who are fitted by training and temperament for work of this kind is limited, but nevertheless Mr. Wiles urged the teaching hospitals to consider most
553
carefully a plan which might be of very great value. In doing so, he reinforced the arguments of Mr. D. H. Patey in his presidential lecture to the society’s section of surgery last year. TIMING OF INSULIN THE effect of insulin on carbohydrate metabolism varies greatly with the interval before food is taken.2 If, for instance, soluble insulin is injected subcutaneously and at the same time glucose 100 g. is taken by mouth, it accelerates glucose assimilation to such an extent that alimentary hyperglycaemia is completely suppressed. If, however,-the insulin precedes the ingestion of glucose by some 40-50 minutes the hypoglycsemia that develops during this interval stimulates the body’s compensatory mechanism so effectively that alimentary hyperglycaemia is greatly increased, and glucose tolerance is so impaired that glycosuria may result even in normal people.2 In diabetics the body’s reaction to hypoglycaemia is exaggerated, and the diabetes may be greatly accentuated for a considerable time. A number of mechanisms participate in this anti-insulin reaction ; and of these the release of adrenaline bv the adrenal medulla and of 11-oxycorticoids by the adrenal cortex stimulated by A.C.T.H. are probably the most important. The role of adrenaline is illustrated by the greater susceptibility to hypoglycaemia of diabetics receiving hexamethonium compounds,3 while the role of the adrenal steroids is illustrated by : (1) patients with rheumatoid arthritis and insulin hypoglycsemia, during which uric-acid excretion is increased and the eosinophil-count falls 4 ; and (2) rats in which the adrenal medulla has been removed, and in which the adrenal ascorbic-acid content falls
after insulin hypoglycaemia.5 The clinical importance of these insulin effects is clear. It would seem wise to recommend the administration of soluble insulin within 15 minutes of the next meal. When used alone, delayed-action insulins, and particularly protamine-zinc insulin, need not be so accurately timed in relation to meals. It is well, however, to give globin insulin /4—1 hour before a meal, because of the long latent interval before it produces its hypoglycaemic effect. INTRASPLENIC GRAFTS OF OVA’ AND OVARIES ACCORDING to a report in the New York Times of March 2, Dr. C. C. Little and his colleagues at the Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, have obtained normal living young mice from ova transplanted into spleens and left for as long as 60 days before being regrafted into ovaries of foster-mothers. The young mice so produced showed no hereditary changes for at least four generations. The purpose of this weird experiment must seem obscure without some knowledge of its forerunners. Previously M. S. Biskind and G. R. Biskind had grafted complete ovaries into spleens of ovariectomised rats. Many of the grafts developed into tumours and some metastasised to the liver. The tumours which arise under these conditions are granulosa-celled growths, luteomas, and mixtures of the two. Li and Gardner7 have obtained these tumours in all strains of mice which they have tested ; and they revealed the autonomous nature of such neoplasms by successfully transplanting some into intact new hosts in which the tumour cells
An essential condition for success in these experiments is bilateral removal of both gonads of the host into whose spleen the new implant is to be made. The Biskinds argued that as the splenic circulation drains into the liver, the hormones carried to it from the grafts will be inactivated. With the hosts’ gonads excised no hormones from that source will oppose the production of pituitary gonadotropin, which will be secreted unopposed and will act continuously on the intrasplenic grafts. The tumours which arise provide a clear-cut example of the tumorigenic action of a hormone under exceedingly artificial conditions. One purpose of the latest experiments thus appears to be to identify the cell of origin of the malignant tumours. Ova, in contrast to ovaries, did not undergo any malignant or other change asjudged by the eventual production from them of normal living mice. Thus the origin of the new formations, whether hyperplasias or neoplasias, must lie, as was supposed, in the cells of the graafian follicle when whole ovaries are used. What is not yet known is the length of time that the ovary must remain continuously exposed to gonadotropin, and the total dose required, before malignant changes appear. The first of these problems is being tackled at Har Harbor TRANSFUSION
EQUIPMENT
committee set up by the International LAST week for Standardisation met in London under Organisation the chairmanship of Sir Alan Drury, F.R.S., to discuss the standardisation of transfusion equipment, particularly the modifications that would have to be made in existing types of equipment to bring about functional interchangeability of transfusion sets and containers. a
France, Norway, Sweden, Denmark, Finland, Holland, and the United Kingdom sent delegates, and New Zealand and India sent observers. The problems facing the committee were substantial. Since 1945 transfusion services have grown apace and have developed many types of equipment, each of which, in the eyes of its designers, is obviously better than all the others. To have aimed at international agreement on one pattern of equipment would have been illusory ; but it was also unnecessary, provided agreement could be reached on certain general principles. The first
unopposed gonadotropin.
problem tackled was that of glass transfusion the essential dimension of which, as regards interchangeability, is the internal neck diameter. It appears that the two most widely used containers have internal neck diameters of 22-5 mm. and 30 mm., and the recommendation was made that transfusion services should adopt either the one or the other. The former type of container is already widely used, the transfusion services of the U.K., Scandinavia, Holland, Belgium, Australia,, Canada, and other countries having adopted it. The 30 mm. bottle is the only bottle for intravenous fluids permitted by law in France, and it is also used to some extent in the U.S.A. Unfortunately the U.S.A. did not send a representative ; so the committee had no first-hand information. The committee then agreed on the general characteristics of the closures to be used for these two containers, and went on to discuss the design of piercing needles, with which transfusion sets should be equipped. Agreement was reached on the essential dimensions of the hubs of such needles, with the result that a general recommendation could be made on the internal diameter of tubing and the dimensions of those parts of the filter chamber, drip-counter, and needle mounts to which the tubing is attached. The committee also decided on a specification for the performance of filters.
1. Lancet, 1951, ii, 875. 2. Somogyi, M. J. biol. Chem. 1951, 193, 859. 3. Laurence, D. R., Stacey, R. S. Lancet, 1951, ii, 1145. 4.Kersley, G. D., Mandel, L., Jeffrey, M. R., Desmarais, M. H. L., Bene, E. Brit. med. J. 1950, ii, 855. 5. Vogt, M. J. Physiol. 1951, 114, 222. 6. Biskind, M. S., Biskind, G. R. Proc. Soc. exp. Biol., N.Y. 1944, 55, 176 ; Ibid, 1945, 59, 4 ; Cancer Res. 1950, 10, 309. 7. Li, M. H., Gardner, W. U. Cancer Res. 1949, 9, 35.
The immediate and most important result, if these recommendations were incorporated in national standards, would be that with any transfusion set (which would be equipped with piercing needles to perforate the rubber closure of the transfusion bottle) one could use any bottle of blood or plasma ; in other words, functional interchangeability would be brought about. Secondly, many of the components of the transfusion set would be internationally interchangeable. But two components
were
no
longer subject
to
The tumours produce oestrogen in sufficient amount, or of such a character, that it is not inactivated in the liver, for the uteri are larger than those of castrate animals.
containers,
Annotations POLIOMYELITIS: A NEW APPROACH IMMUNISATION against virus diseases has had its two great successes with smallpox and yellow fever, against each of which living " attenuated " virus is used. In contrast, immunisation with inactivated viruses against such diseases as influenza and mumps has been much With poliomyelitis, however, both less successful. types of approach have been followed. Morgan1 has shown that immunisation of monkeys by parenteral inoculation with inactivated poliomyelitis virus produces serum antibody in high titre and some resistance to challenge with virulent virus. There are, however, two serious obstacles to applying this experimental finding to man : first, poliomyelitis virus cannot be readily purified from the normal constituents of nervous tissue, which are known to produce allergic encephalitis ; and secondly, as in many fields, there is the difficulty of finding enough animals to produce enough virus for man’s demands. On the other hand, the use of a multiplying attenuated virus for immunisation in man is at least feasible. Howe and Bodian2 have infected chimpanzees by feeding them with poliomyelitis virus ; and Melnick and Horstmann3 have shown that such animals become intestinal carriers, excrete virus in their stools, develop serum antibody, and resist reinfection. In his Herter lectures Burnet4 said : "
The logical approach from the ecological angle toward prevention of poliomyelitis is either to find acceptable of ensuring a reasonable transfer of intestinal means infections between children in infancy or to devise some the
of effective immunisation. The technical difficulties a dead virus vaccine seem at the present to be insurmountable, and I feel confident that sooner or later it will become necessary to use living vaccines given by mouth in infancy, perhaps under cover of gamma globulin means
of
obtaining
passive protection." The way to experiments in human immunisation lay open; but who would have the courage to bell the cat ? Koprowski and his associates,5 in a most important paper, describe the results of feeding live poliomyelitis virus of low virulence to 20 volunteers. The virus which they used was prepared from the brain and spinal cord of cotton-rats infected with a rodent-adapted strain of poliomyelitis virus. In none of the 20 were signs or symptoms of illness noted, despite strict watch for any rise of temperature or evidence of gastro-intestinal or neurological disturbance. Most of the volunteers, however, became intestinal carriers of virus ; and all who were not initially immune developed antibodies in their blood to the homologous Lansing type viruses, but not to the heterologous Brunhilde type viruses which seem to be the commonest type isolated at present from cases of poliomyelitis. All interested in poliomyelitis will await further developments of this work with very great interest. But Koprowski and his colleagues are careful to point out that discussion of immunisation by oral administration of poliomyelitis virus is best deferred until this procedure is proved safe. Attenuated organisms of all three immunological types of poliomyelitis virus might be required ; and the brilliant work of Enders et al. in growing the virus in tissue cultures may help to furnish this. Koprowski et al. tell us in a footnote that for obvious reasons the age, sex, and physical status of each volunteer The reasons must be more obvious are not mentioned. to the authors than to the reader, who can only guess, Morgan, I. M. Amer. J. Hyg. 1948, 48, 394. Howe, H. A., Bodian, D. J. exp. Med. 1945, 81, 247. Melnick, J. L., Horstmann, D. M. Ibid, 1947, 85, 287. Burnet, F. M. Bull. Johns Hopk. Hosp. 1951, 88, 119. Koprowski, H., Jervis, G. A., Norton, T. W. Amer. J. Hyg 1952, 55, 108. 6. Enders, J. F., Weller, T. H., Robbins, F. C. Science, 1949 109, 85.
1. 2. 3. 4. 5.
from the methods used for feeding the virus, that the volunteers were very young and that the volunteering One of the reasons for the was done by their parents. richness of ,the English language is that the meaning of some words is continually changing. Such a word is " volunteer." We may yet read in a scientific journal that an experiment was carried out with twenty volunteer mice, and that twenty other mice volunteered as controls.
ORTHOPÆDIC JUDGMENT WHEREAS in many other branches of surgery the saving of life must be the paramount concern, the success of an orthopaedic operation is judged by the extent to which the patient is rid of his pain and relieved of his disability. It is this distinction, said Mr. Philip Wiles in his presidential address to the section of ortho. paedics of the Royal Society of Medicine on March 4, that lays upon the orthopaedic surgeon a special responsi. bility when he advises a patient to undergo an operation. The surgeon must be particularly confident that the patient will emerge an abler and more comfortable body than before ; that his improvement will justify the ordeal ; and that the risk of surgery is a reasonable one in the circumstances. The apparently irrational fears of the patient should be respected : it is too often disastrous to persuade an unwilling person to have an operation. Since it is our aim, said Mr. Wiles, to relieve symptoms, it is the sufferer who must finally weigh the risk and balance his apprehensions against the probable gain. Moreover, it is easy to say : " Come into hospital and I’ll put you right in no time " ; but what is the cost to a man and his familyg He may have been able to continue work despite, for example, a prolapsed intervertebral disc. How often, Mr. Wiles asked his audience, have you seen that same man six or twelve months after operation when he was still not back at his old work ? For the completely incapacitated the risk may be justified, but who shall judge in other circumstances! The right time for operation is when the patient knows the dangers and is willing, and indeed anxious, to face them. But Mr. Wiles thought that the hardest thing of all is to give a proper estimate of the benefit which may reasonably be expected from operation. There are so many variables : on the one hand, the personality of the patient, his threshold for pain, and his cooperation; on the other, his physical condition and the response of his tissues to the operation and the subsequent reablement. The answer is a guess, though it is a guess which becomes more and more accurate as the experience of the surgeon grows. Turning to the opportunities for the younger man, Mr. Wiles remarked that, while instruction in the actual techniques of orthopaedics is not hard to get, it is none too easy nowadays to acquire the essential basic training in general surgery. Rapid specialisation has changed the pattern and character of surgery in the last twenty or thirty years. " How is the surgeon in training to obtain a sufficiently varied experience now that the general surgical wards no longer contain a representative cross-section of surgical practice ?" he asked. And " how should the surgical beds of a teaching hospital be divided to give sufficient representation to the " specialties and yet maintain a proper balance Both questions could in part be answered, he thought, by giving the specialised surgeon a larger share in the teaching of basic surgery and by allotting him certain of the teaching beds now labelled " general surgery." Thus a student would spend, say, three months of a six months’ surgical appointment with a genito-urinary, an orthopaedic, or a rectal surgeon, who would use his special cases to illustrate surgical principles. The number of men who are fitted by training and temperament for work of this kind is limited, but nevertheless Mr. Wiles urged the teaching hospitals to consider most
553
carefully a plan which might be of very great value. In doing so, he reinforced the arguments of Mr. D. H. Patey in his presidential lecture to the society’s section of surgery last year. TIMING OF INSULIN THE effect of insulin on carbohydrate metabolism varies greatly with the interval before food is taken.2 If, for instance, soluble insulin is injected subcutaneously and at the same time glucose 100 g. is taken by mouth, it accelerates glucose assimilation to such an extent that alimentary hyperglycaemia is completely suppressed. If, however,-the insulin precedes the ingestion of glucose by some 40-50 minutes the hypoglycsemia that develops during this interval stimulates the body’s compensatory mechanism so effectively that alimentary hyperglycaemia is greatly increased, and glucose tolerance is so impaired that glycosuria may result even in normal people.2 In diabetics the body’s reaction to hypoglycaemia is exaggerated, and the diabetes may be greatly accentuated for a considerable time. A number of mechanisms participate in this anti-insulin reaction ; and of these the release of adrenaline bv the adrenal medulla and of 11-oxycorticoids by the adrenal cortex stimulated by A.C.T.H. are probably the most important. The role of adrenaline is illustrated by the greater susceptibility to hypoglycaemia of diabetics receiving hexamethonium compounds,3 while the role of the adrenal steroids is illustrated by : (1) patients with rheumatoid arthritis and insulin hypoglycsemia, during which uric-acid excretion is increased and the eosinophil-count falls 4 ; and (2) rats in which the adrenal medulla has been removed, and in which the adrenal ascorbic-acid content falls
after insulin hypoglycaemia.5 The clinical importance of these insulin effects is clear. It would seem wise to recommend the administration of soluble insulin within 15 minutes of the next meal. When used alone, delayed-action insulins, and particularly protamine-zinc insulin, need not be so accurately timed in relation to meals. It is well, however, to give globin insulin /4—1 hour before a meal, because of the long latent interval before it produces its hypoglycaemic effect. INTRASPLENIC GRAFTS OF OVA’ AND OVARIES ACCORDING to a report in the New York Times of March 2, Dr. C. C. Little and his colleagues at the Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine, have obtained normal living young mice from ova transplanted into spleens and left for as long as 60 days before being regrafted into ovaries of foster-mothers. The young mice so produced showed no hereditary changes for at least four generations. The purpose of this weird experiment must seem obscure without some knowledge of its forerunners. Previously M. S. Biskind and G. R. Biskind had grafted complete ovaries into spleens of ovariectomised rats. Many of the grafts developed into tumours and some metastasised to the liver. The tumours which arise under these conditions are granulosa-celled growths, luteomas, and mixtures of the two. Li and Gardner7 have obtained these tumours in all strains of mice which they have tested ; and they revealed the autonomous nature of such neoplasms by successfully transplanting some into intact new hosts in which the tumour cells
An essential condition for success in these experiments is bilateral removal of both gonads of the host into whose spleen the new implant is to be made. The Biskinds argued that as the splenic circulation drains into the liver, the hormones carried to it from the grafts will be inactivated. With the hosts’ gonads excised no hormones from that source will oppose the production of pituitary gonadotropin, which will be secreted unopposed and will act continuously on the intrasplenic grafts. The tumours which arise provide a clear-cut example of the tumorigenic action of a hormone under exceedingly artificial conditions. One purpose of the latest experiments thus appears to be to identify the cell of origin of the malignant tumours. Ova, in contrast to ovaries, did not undergo any malignant or other change asjudged by the eventual production from them of normal living mice. Thus the origin of the new formations, whether hyperplasias or neoplasias, must lie, as was supposed, in the cells of the graafian follicle when whole ovaries are used. What is not yet known is the length of time that the ovary must remain continuously exposed to gonadotropin, and the total dose required, before malignant changes appear. The first of these problems is being tackled at Har Harbor TRANSFUSION
EQUIPMENT
committee set up by the International LAST week for Standardisation met in London under Organisation the chairmanship of Sir Alan Drury, F.R.S., to discuss the standardisation of transfusion equipment, particularly the modifications that would have to be made in existing types of equipment to bring about functional interchangeability of transfusion sets and containers. a
France, Norway, Sweden, Denmark, Finland, Holland, and the United Kingdom sent delegates, and New Zealand and India sent observers. The problems facing the committee were substantial. Since 1945 transfusion services have grown apace and have developed many types of equipment, each of which, in the eyes of its designers, is obviously better than all the others. To have aimed at international agreement on one pattern of equipment would have been illusory ; but it was also unnecessary, provided agreement could be reached on certain general principles. The first
unopposed gonadotropin.
problem tackled was that of glass transfusion the essential dimension of which, as regards interchangeability, is the internal neck diameter. It appears that the two most widely used containers have internal neck diameters of 22-5 mm. and 30 mm., and the recommendation was made that transfusion services should adopt either the one or the other. The former type of container is already widely used, the transfusion services of the U.K., Scandinavia, Holland, Belgium, Australia,, Canada, and other countries having adopted it. The 30 mm. bottle is the only bottle for intravenous fluids permitted by law in France, and it is also used to some extent in the U.S.A. Unfortunately the U.S.A. did not send a representative ; so the committee had no first-hand information. The committee then agreed on the general characteristics of the closures to be used for these two containers, and went on to discuss the design of piercing needles, with which transfusion sets should be equipped. Agreement was reached on the essential dimensions of the hubs of such needles, with the result that a general recommendation could be made on the internal diameter of tubing and the dimensions of those parts of the filter chamber, drip-counter, and needle mounts to which the tubing is attached. The committee also decided on a specification for the performance of filters.
1. Lancet, 1951, ii, 875. 2. Somogyi, M. J. biol. Chem. 1951, 193, 859. 3. Laurence, D. R., Stacey, R. S. Lancet, 1951, ii, 1145. 4.Kersley, G. D., Mandel, L., Jeffrey, M. R., Desmarais, M. H. L., Bene, E. Brit. med. J. 1950, ii, 855. 5. Vogt, M. J. Physiol. 1951, 114, 222. 6. Biskind, M. S., Biskind, G. R. Proc. Soc. exp. Biol., N.Y. 1944, 55, 176 ; Ibid, 1945, 59, 4 ; Cancer Res. 1950, 10, 309. 7. Li, M. H., Gardner, W. U. Cancer Res. 1949, 9, 35.
The immediate and most important result, if these recommendations were incorporated in national standards, would be that with any transfusion set (which would be equipped with piercing needles to perforate the rubber closure of the transfusion bottle) one could use any bottle of blood or plasma ; in other words, functional interchangeability would be brought about. Secondly, many of the components of the transfusion set would be internationally interchangeable. But two components
were
no
longer subject
to
The tumours produce oestrogen in sufficient amount, or of such a character, that it is not inactivated in the liver, for the uteri are larger than those of castrate animals.
containers,