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LABORATORY ANIMALS BUREAU
144 when 3 pints of blood was transfused instead of 2 pints. This effect of failure of the haemoglobin to release its Valtis oxygen properly is quantitatively significant. and Kennedy transfused 3 pints of blood into a patient with an initial haemoglobin level of 35% (5-2 g. per 100 ml.), and the patient’s hsemoglobin was raised to " 55% (8-1 g. per 100 ml.) ; but the " shift to the left of the oxygen dissociation curve meant that at an oxygen partial pressure of 40 mm. Hg (a normal pressure for most tissues) only 20% of the oxygen carried was released to the tissues, instead of the normal 40%. The effect, however, lasts only a few hours ; it begins to decrease after about 6 -hours and has largely passed off after 24 hours, though differences can still be detected for several days. The effect may also be more than compensated for by the rise in haemoglobin level and therefore in the total amount of oxygen transported. Here again Valtis and Kennedy found that by adding sodium chloride to the blood before transfusion, to give a final concentration of 0.45%, the effect on the oxygen dissociation curve could be totally prevented. Valtis and Kennedy have sought the cause of this disturbance of oxygen-releasing capacity of stored blood, and they conclude that it is alteration in the pH of the red cells and in the electrolytic and osmotic relations between the cells and the plasma of the transfused blood. Whether this relatively transient diminution of functional capacity of transfused blood is important enough to make the blood-transfusion experts reconsider the efficiency of the standard acid-citrate/dextrose medium is uncertain. The addition of sodium chloride to the blood just before it is transfused does not seem a very practical measure, and in the severely anaemic patient any addition to the inert volume of fluid to be transfused must be looked at askance. LABORATORY ANIMALS BUREAU IN the years 1939-51 the number of animals used in British laboratories increased from about a million to nearly two million, and the annual cost of providing such animals rose to £ 200,000 a year.1 In 1947 the Medical Research Council set up the Laboratory Animals Bureau, with the general object of helping the laboratory worker to obtain suitable animals for his investigations. The bureau’s first task was to survey the sources and uses of laboratory animals ; and though these surveys are not yet complete it is already possible to see where the need for improvement lies. Thus the bureau launched, in 1950, a scheme for accrediting commercial breeders of guineapigs, mice, and rabbits.2 It arranges annual congresses for animal technicians ; and at the third of these, in 1950, the Animal Technicians Association was founded. It has established a central advisory service on the care, management, and breeding of laboratory animals, and on the design of animal houses and
equipment. The bureau
half-yearly News Letter, technical specific subjects, and a bulletin for accredited breeders ; and it provides regular information about the availability of animals for laboratory use. In 1951 it took over the production and distribution of the Mouse publishes
notes and memoranda
a
on
News Letter. More recently it has issued the first volume of Collected Papers, a new annual mainly devoted to reporting its annual symposium ; and a Catalogue of Uniform Strains of Laboratory Animals Maintained in Great Britain.3
very necessary groundwork for a new and Britain is unique in providing its scientists with such a service. So far the bureau has been mainly occupied with administrative, advisory, and " post office " work. Some investigations have been
All this
was
organisation ;
1. L.A.B. Collected Papers, 1953, 1, 7. 2. Mon. Bull. Min. Hlth Lab. Serv. 1953, 12, 165. 3. All these publications are obtainable from the Animals Bureau, M.R.C. Laboratories, Holly Hill, London, N.W.3.
Laboratory Hampstead,
carried out, but the staff is small and the unit is not equipped to deal with large-scale research problems. The scope of the bureau could usefully be enlarged to enable it to undertake more systematic research on feeding, accommodation, disease control, and quantity production of highly uniform animals. In its first six years it has effectively brought about the dissemination of existing information. Perhaps in its second six years it will be granted resources with which to learn more about how to choose and obtain the right animal, and in particular the most suitable strain. METABOLISM IN OBESITY
ABILITY to treat obesity by some means other thana strictly enforced diet would be welcome. Pennington, to whose work we have already briefly referred,1 advocates a liberal diet of meat and fat in which only carbohydrate is restricted.2-7 He believes that the obese do not oxidise fat freely when carbohydrate is present in the diet; they cannot withdraw fat normally from their depots, and in order to meet their needs for energy they eat more food than normal. He also claims that on a low-calorie diet their metabolic-rate, and their output of energy, fall as in normal people who are starved ; consequently, treatment by dietary restriction becomes less effective and the patient feels ill. On the other hand, according to Pennington, a carbohydrate-free, and therefore ketogenic, diet compels the oxidation of fat. This, he says, may increase metabolism to such an extent that " some obese individuals must, of necessity, lose weight on an intake of 3000 calories or more per day."’7 Appetite may be reduced, since more energy is now being drawn from the body’s stores. Pennington has hardly proved his case. There is no direct evidence that the obese cannot oxidise fat. Pennington rejects Newburgh’sfinding that the obese mobilise fat as readily as normal people and that their metabolic-rate is not measurably altered by changes in the calorie intake. His own conclusion that their output of energy varies with the diet is based on published work, some of which was interpreted differently by the original authors. Pennington has so far produced little evidence of his own. He has reported 20 cases. On his regimen the patients, who weighed up to 20 stone at the outset, lost an average of 21 pounds in three and a half months 2; and their weight remained stationary during the following year.3 A loss of weight of this order might result from imposing any unaccustomed diet,1 and is similar to that found by Dole and his associates after change from a normal diet to one low in protein.9The exclusion of salt from Pennington’s diet may have contributed part of the effect.100 There is still no published evidence that any diet giving unrestricted and liberal calories can produce a continued loss of weight, as opposed to an initial loss followed by stabilisation at a lower, but still abnormal, level. It is certainly true that the metabolism of fatty tissue must be considered in relation to obesity-and so, too (at least in relation to overweight) must watersalt metabolism, as Professor Zondek has lately pointed out Fat-cells are not inert receptacles : they are engaged in a continuous metabolic exchange, so their content of fat depends on the balance between what enters and leaves them.12 Quite possibly this balance may for a time be displaced in the direction of excessive See Lancet, 1953, ii, 126. Pennington, A. W. Industr. Med. 1949, 18, 259. Pennington, A. W. Delaware St. med. J. 1951, 23, 79. Pennington, A. W. New Engl. J. Med. 1953, 248, 959. Pennington, A. W. J. clin. Nutr. 1953, 1, 100. Pennington, A. W. Ibid, p. 343. Pennington, A. W. Amer. J. dig. Dis. 1953, 20, 268. Newburgh, L. H. Arch. intern. Med. 1942, 70, 1033. Dole, V. P., Dahl, L. K., Schwartz, I. L., Cotzias, G. C., Thaysen, J. H., Harris, C. J. clin. Invest. 1953, 32, 185. 10. Anderson, A. B. Quart. J. Med. 1944, 37, 27. 11. Zondek, H. Lancet, Jan. 2, 1954, p. 49. 12. Wertheimer, E., Shapiro, B. Physiol. Rev. 1948, 28, 451. 1. 2. 3. 4. 5. 6. 7. 8. 9.
equipment. The bureau
half-yearly News Letter, technical specific subjects, and a bulletin for accredited breeders ; and it provides regular information about the availability of animals for laboratory use. In 1951 it took over the production and distribution of the Mouse publishes
notes and memoranda
a
on
News Letter. More recently it has issued the first volume of Collected Papers, a new annual mainly devoted to reporting its annual symposium ; and a Catalogue of Uniform Strains of Laboratory Animals Maintained in Great Britain.3
very necessary groundwork for a new and Britain is unique in providing its scientists with such a service. So far the bureau has been mainly occupied with administrative, advisory, and " post office " work. Some investigations have been
All this
was
organisation ;
1. L.A.B. Collected Papers, 1953, 1, 7. 2. Mon. Bull. Min. Hlth Lab. Serv. 1953, 12, 165. 3. All these publications are obtainable from the Animals Bureau, M.R.C. Laboratories, Holly Hill, London, N.W.3.
Laboratory Hampstead,
carried out, but the staff is small and the unit is not equipped to deal with large-scale research problems. The scope of the bureau could usefully be enlarged to enable it to undertake more systematic research on feeding, accommodation, disease control, and quantity production of highly uniform animals. In its first six years it has effectively brought about the dissemination of existing information. Perhaps in its second six years it will be granted resources with which to learn more about how to choose and obtain the right animal, and in particular the most suitable strain. METABOLISM IN OBESITY
ABILITY to treat obesity by some means other thana strictly enforced diet would be welcome. Pennington, to whose work we have already briefly referred,1 advocates a liberal diet of meat and fat in which only carbohydrate is restricted.2-7 He believes that the obese do not oxidise fat freely when carbohydrate is present in the diet; they cannot withdraw fat normally from their depots, and in order to meet their needs for energy they eat more food than normal. He also claims that on a low-calorie diet their metabolic-rate, and their output of energy, fall as in normal people who are starved ; consequently, treatment by dietary restriction becomes less effective and the patient feels ill. On the other hand, according to Pennington, a carbohydrate-free, and therefore ketogenic, diet compels the oxidation of fat. This, he says, may increase metabolism to such an extent that " some obese individuals must, of necessity, lose weight on an intake of 3000 calories or more per day."’7 Appetite may be reduced, since more energy is now being drawn from the body’s stores. Pennington has hardly proved his case. There is no direct evidence that the obese cannot oxidise fat. Pennington rejects Newburgh’sfinding that the obese mobilise fat as readily as normal people and that their metabolic-rate is not measurably altered by changes in the calorie intake. His own conclusion that their output of energy varies with the diet is based on published work, some of which was interpreted differently by the original authors. Pennington has so far produced little evidence of his own. He has reported 20 cases. On his regimen the patients, who weighed up to 20 stone at the outset, lost an average of 21 pounds in three and a half months 2; and their weight remained stationary during the following year.3 A loss of weight of this order might result from imposing any unaccustomed diet,1 and is similar to that found by Dole and his associates after change from a normal diet to one low in protein.9The exclusion of salt from Pennington’s diet may have contributed part of the effect.100 There is still no published evidence that any diet giving unrestricted and liberal calories can produce a continued loss of weight, as opposed to an initial loss followed by stabilisation at a lower, but still abnormal, level. It is certainly true that the metabolism of fatty tissue must be considered in relation to obesity-and so, too (at least in relation to overweight) must watersalt metabolism, as Professor Zondek has lately pointed out Fat-cells are not inert receptacles : they are engaged in a continuous metabolic exchange, so their content of fat depends on the balance between what enters and leaves them.12 Quite possibly this balance may for a time be displaced in the direction of excessive See Lancet, 1953, ii, 126. Pennington, A. W. Industr. Med. 1949, 18, 259. Pennington, A. W. Delaware St. med. J. 1951, 23, 79. Pennington, A. W. New Engl. J. Med. 1953, 248, 959. Pennington, A. W. J. clin. Nutr. 1953, 1, 100. Pennington, A. W. Ibid, p. 343. Pennington, A. W. Amer. J. dig. Dis. 1953, 20, 268. Newburgh, L. H. Arch. intern. Med. 1942, 70, 1033. Dole, V. P., Dahl, L. K., Schwartz, I. L., Cotzias, G. C., Thaysen, J. H., Harris, C. J. clin. Invest. 1953, 32, 185. 10. Anderson, A. B. Quart. J. Med. 1944, 37, 27. 11. Zondek, H. Lancet, Jan. 2, 1954, p. 49. 12. Wertheimer, E., Shapiro, B. Physiol. Rev. 1948, 28, 451. 1. 2. 3. 4. 5. 6. 7. 8. 9.