Current
Topics patient should begin with a daily dose of 10 g. of succinic acid, that this dosage should be maintained until 1 or 2 days after disappearance of the acetonuria, and that it should then be gradually reduced. The acid is given after meals as a 2 per cent solution in tapwater, the total dose being divided throughout the day. Unfortunately it is apt to produce severe nausea, and causes distress especially to patients with hyperacidity, so that experiments are now being made with its administration in capsules, or as the calcium salt in powder form. Szent-Gyorgyi provides an explanation of these findings in terms of tissue metabolism. During the last few years he has developed a theory that the respiration of tissues is catalyzed by certain C4-dicarboxylic acids, of which succinic acid is one. He now claims that in particular the oxidation of pyruvic acid, an intermediary substance in the metabolism of carbohydrates, is catalyzed by these C4 acids. He further states that if for any reason this catalysis fails, the pyruvic acid is not oxidized, but is instead converted into acetone bodies. (That such a conversion can occur has indeed been known for many years.) He therefore suggests that the ketosis of diabetes is due to failure of the C4 acids to catalyze the oxidation of pyruvic acid, this failure probably being due to a shortage of C4-dicarboxylic acids in diabetes, either because their formation is inhibited or because their destruction is accelerated. Administration of small amounts of a C4-acid, such as succinic acid, might thus, it is argued, restore catalysis of the pyruvic acid oxidation and so stop the formation of acetone bodies. Whether this argument will prove acceptable cannot be decided before publication of the evidence on which it rests. From the clinical standpoint, however, it is clear that if others have the same experiences as Koranyi and SzentGyorgyi a substantial advance will have been made in improving the lot of the diabetic. Succinic acid is cheap, and the advantage of its being given by mouth needs no emphasis. If the dose of insulin can be new
A New
Remedy
for Diabetic Ketosis
(From the Lancet, 24th July, 1937, Vol. II, p. 200) Professor Szent-Gyorgyi's record as an investigator immediate attention for his latest and most exciting observations. In brief, an idea springing from his studies of tissue metabolism led him to try the effect of succinic acid as a remedy for the ketosis of diabetes. Only five patients have so far been treated, but in one of these it was found that as little as 1.0 gramme daily by mouth would remove ketosis, the acetone bodies disappearing completely from the urine and the alkali reserve rising. In one of these cases the patient had suffered from diabetes for several years and had been kept free from ketonuria and glycosuria by a carefully controlled diet and 70 units of insulin daily. But even this treatment had failed in the long run, and just before her treatment with succinic acid her symptoms were severe, with a blood-sugar of 352 mg. per 100 c.cm., and an alkali reserve of 25 vols, per cent. Koranyi and Szent-Gyorgyi discontinued the insulin injections, and gave instead 10 g. of succinic acid per day orally. By the fourth day, though the concentration of sugar in the urine was unaltered, acetone bodies had disappeared from the urine, and later the alkali reserve That this remarkable was found to have risen sharply. result was not merely fortuitous was shown on two occasions by return of ketosis when use of the acid was stopped for a few days. Finally it proved possible to reduce the dose of succinic acid to 1.0 g. per day, and at the same time the urine could be kept sugar-free by the simultaneous administration of 10 units of insulin daily?in contrast to the 70 units previously given. Though this was the most striking of the five cases the others also yielded evidence of the antiketogenic effect of the acid. In announcing these results at an early stage Koranyi and Szent-Gyorgyi wish the possibilities of their method to be explored by others. From their brief experience they suggest that the treatment of a ensures
752
THE INDIAN MEDICAL GAZETTE
reduced when succinic acid is given at the same time, a great saving will be effected; and the use of one of the new combinations of insulin with a prolonged action might mean that the dosage could be kept at a very low level indeed.
Nutritional Needs in Pregnancy * By Sir ROBERT McCARRISON,
m.d., f.r.c.f.
(Retd.) (From the British Medical Journal, 7th August, 1937, Vol. II, p. 256) Last year at the inaugural meeting of the Section of Nutrition in Oxford, I ventured to predict that the day was not far distant when, instead of one morning being devoted to its work, it would rank with the Section of Medicine as a three-day fixture. To-day my prediction MAJOR-GENERAL, I.M.S.
is two-thirds of the way towards fulfilment. And it is perhaps fitting that the Section of Obstetrics and Gynaecology should be the first to ally itself with that of Nutrition. By this alliance and by the application of the principles of nutrition to the mothers of our race and to their children we begin at the beginning to lay the foundations of a more healthful existence for our people?a finer structure of national' health. For, as Carrell has recently reminded us, nutrition is synonymous with existence'; synonymous, that is to say, with the act of living, with the exercise of the vital functions. To this I would add that faulty nutrition is synonymous with faulty existence, with the faulty exercise of the vital functions. For the student of nutrition there is no more enlightening experience than to observe the behaviour of cells under cultural conditions in vitro. Soon lie perceives that their growth, their reproduction, their structure, and their functions depend not only on the composition of the fluid medium in which they are immersed but on the removal from it of the waste products of their activities. So it is with the human body; that vast aggregation of cells, living, moving, and having their being within the closed circuit of the blood stream. For them the continual purification of the fluid medium in which they live is as necessary to their well-being as its continual enrichment with essential nutrients. It is to these two ends that the processes involved in the function of nutrition are directed and co-ordinated. Inspiration, mastication, deglutition, digestion, absorption, and circulation; these are the supply services. Exhalation, perspiration, urinary excretion, and defalcation: these are the sanitary services. The central act?assimilation?in the series of processes involved in nutrition is a function of living matter, dependent on the efficiency of the supply services on the one hand and on that of the sanitary services on the other. To the cell belongs the task of nourishing itself; to us, as physicians, belongs the task of enabling it to do so by our supervision of the efficiency of these two services. Nutrition, then, is the sum of the acts or processes by which the structure and functions of all organs and parts of the body?including, of course, those that subserve the function of reproduction?are established and maintained. It is, in short, that function of the body by which health is maintained: health, which implies the ability to produce and rear offspring fitted to live and efficiently to perform the functions of their species. Continued efficiency of the function of nutrition It is customary to speak of nutrition in pregnancy as though it differed in some directions?in the supply of certain food essentials, for instance?from nutrition of other periods of life. Indeed, the very title of our subject suggests such a distinction. It is customary also to speak of pregnancy as though it involved an additional burden on the maternal organism, as, unfortunately, it often does. But I suggest to you that the * Read in opening a discussion at a joint, meeting of ihe Sections of Nutrition and Obstetrics and Gynaecology at the Annual Meeting of the British Medical Association, Belfast, 1937.
[Dec.,
1937
nutritional needs in pregnancy are those necessary to the continued efficiency of the function of nutrition throughout life. For in this efficiency the efficiency of that other fundamental function of the body?reproduction ?is inherent. As well might we regard the taking of a steep hill as a feat additional to the normal function of a motor car as regard the making of a seven-pound baby as a feat additional to the normal function of woman. The properly constructed car, the properly adjusted, oiled, greased, fuelled, and tended car takes the hill in its stride; the properly constructed, adjusted, fuelled, and tended woman takes pregnancy in hers. It is this construction, this adjusting, this fuelling, this tending, that, in the perfection of its operation, the function of nutrition effects. But the case is different with the ill-constructed, the ill-adjusted, the ill-tended woman, in whom the function of nutrition from infancy onwards has been faulty. Then, indeed, pregnancy becomes a feat to which some succumb and from which many emerge with some weakness exposed, some permanent damage incurred. It is not, however, with the ill-constructed, the ill-adjusted, the ill-nourished, the ill-conditioned that I am here concerned, but with the Rolls-Royce of womanhood, or for that matter with the dependable Baby Austin or Morris Minor. It is to the production of these?aye, to their mass-production? that we must direct our energies, though the salvaging, the patching-up, of wrecks must still remain our portion. The nutritional needs in pregnancy are, I repeat, those necessary to the efficiency of the function of nutrition. Their satisfaction must begin not with conception but with the antenatal life of the mothers of our race. It must continue throughout the period of their growth and development up to, during, and following the period when they find their fulfilment in motherhood: a fulfilment for which nutrition prepares and makes ready the way?sometimes well, sometimes ill, according to its perfection or imperfection. It is impossible to dissociate reproduction from nutrition. It is impossible to dissociate reproduction from the acts and processes involved in nutrition. Respiration, digestion, absorption, secretion, circulation, assimilation, excretion: these are prologues to the crowning act of the imperial theme of motherhood. Four
things
needful
the things needful to the efficiency of the function of nutrition? They are: First, the adequate provision of the materials with which this function is effected: oxygen, water, properly constituted food, and a substance or substances produced in the skin by the action of sunlight. Second, the efficient performance of each one of the acts or processes involved in nutrition, these acts or processes being themselves dependent on the proper nourishment of the organs and tissues performing them. Third, the practice of measures and habits of life favourable to the efficiency of the function of nutrition: appropriate exercise in the open air, proper breathing, agreeable mental occupation, promotion of the function of the skin by bathing, suitable clothing, and exposure of parts of the body to such sunlight as is available, promotion of the action of the kidneys and bowels by proper food and the free consumption of water. Fourth, the avoidance of all influences that adversely affect the function of nutrition: such, for instance, as insufficient rest and want of sleep, bad ventilation, insanitary conditions generally, worry, emotional excitement, constipation, alcohol, and infection. These are the nutritional needs in pregnancy as they are the nutritional needs of the body throughout life. Their satisfaction makes of pregnancy one of the happiest, the most healthful, periods of a woman's life.
What, then,
are
Dietetic requirements in pregnancy This brings me to that section of our subject which, to judge by the programme before us, is to occupy the remainder of this morning's session: dietetic requirements in pregnancy. I shall not attempt to discuss these requirements in detail, but will content myself with an enumeration of the foodstuffs which, if properly
CURRENT TOPICS
Dec., 1937]
and properly combined, provide all the food essentials the prospective mother needs. These foodstuffs are, in order of precedence: (1) Milk and the products of milk (butter, cheese, skimmed milk, buttermilk). (2) Whole or lightly milled cereal grains; in particular a good wholemeal bread or standard bread, and oatmeal. (3) Green and leafy vegetables. (4) Root vegetables, particularly potatoes, carrots, and onions. (5) Fruit, including the tomato. (6) Pulses. (7) Egg. (8) Meat, including fish, fowl, and glandular organs. To these there must in this country be added cod-liver oil, not in the large doses commonly prescribed but in the sufficient dose of a teaspoonful daily. And as an additional assurance of functional efficienc}' of blood, muscle, and nerve, a portion of yeast extract is a wise precaution. Those of you who have studied the revised report of the Technical Commission appointed by the League of Nations to define the nutritional needs of the human being in the course of development from conception to adult age will be aware that it is from these foodstuffs that the Commission prepared their dietary schedules for all periods of life up to and including pregnancy. They had in mind, no doubt, the preparation of the female of the human species for motherhood.
produced, properly treated,
Animal protein: wholemeal bread One revision of this report has been made, and 1 hope that the next one, already foreshadowed, will remove what, in my opinion, are three blemishes on its excellence. The first of these is the unnecessarily high amount of animal protein (68 grammes out of a total protein content of 105 grammes) it prescribes. The 40 grammes provided by milk and cheese are sufficient? though an additional 10 grammes may be provided by liver, fish, or meat?sufficient, that is to say, if whole cereal or lightly milled cereals be used instead of highly milled ones and if more green-leaf vegetables be included in the diet. Phj'siological as well as economic prudence forbids a greater intake of animal protein than is needful. My second criticism is the insufficient insistence on the use of wholemeal bread. ' White flour in the process of milling is deprived of important nutritive elements. Its use should be decreased and partial substitution by lightly milled cereals, and especially potatoes, is recommended'. The exhortation is well enough so far as it goes. But it is complete, not partial, substitution that must, in my view, be at all times and in all places insisted upon. For the important nutritive elements of which white flour is deprived include the_ vitamin-B complex, vitamin E, an unidentified hemopoietic factor, the proteins of the germ and bran which are of relatively high nutritive value and so constituted as to supplement those of the interior of the grain, and fibre, which is of particular merit in ensuring the efficient action of the bowels. It is folly to deprive bread?the staff of life?of nutritive elements so important to the well-being of the body, whether in pregnancy or at other periods of life.
/
Fresh vegetables and fruit The third criticism that I have to offer is the relative paucity of fresh green vegetables and raw ripe fruit in the dietary schedule. These should form a large part of the daily diet. It is not alone for their vitamin-C content that they are of such value, but for their proteins which, though small in amount, are of high biological value, for their mineral contents, and for their utility in maintaining the balance between alkaliyielding and ingredients of the food.
acid-yielding
The Transfusion of Stored Cadaver Blood By Professor W. N. SHAMOV (From the Lancet, 7th August, 1937, Vol. II, p. 30G) It is well known that the death of
an
animal by
no
means involves a simultaneous death of all its tissues and organs. For instance, the muscles removed from
the body of
a
recently killed animal remain contractile
^
for several hours; other examples include the heart, the the endocrine blood-vessels, and glands. Death therefore, is only the moment of destruction of an intricate complex of connections and mutual relations between the separate tissues of an organism, which retain their full vitality and function for a varying time. The time depends chiefly on how far the artificial conditions are able to satisfy their fundamental requirements of nutrition and the removal of the products of metabolism. The most elementary of these conditions are shown by tissiie cultures, which may grow in vitro for an unlimited time so long as they are periodically washed and transplanted on new nutritive media. But the vitality of such organs as the heart requires for its support a very much more complicated environment which it is difficult to create artificially, and they can exist in vitro for only a comparatively short time. The ideal conditions, of course, would be found only in another living organism where all the processes of nutrition and metabolism are accurately regulated. A good example of this is given by blood transfusion, where the blood of one animal after long preservation in vitro can be successfully transfused into another, and continue to accomplish all its fundamental functions. From this an extremely interesting question arises: Could not some tissues or organs from the dead body be transferred to the living and continue to function normally? Can a defect in a living body be remedied by the transplantation of tissue from the dead, already doomed soon to perish? The solution of this problem would not only be of the greatest biological interest but might also disclose wide prospects for practical surgery. Preliminary
experiments
As the object of my first researches in this direction I selected the blood, since more is known about the method of its transference, and all the destructive processes that develop after death have a greater influence on it than is the case in any other tissue. Against this there is the weighty objection that an abundant bacterial flora may enter the blood stream even during the last agony, and that, moreover, it must contain a great quantity of toxic substances as the result of death and the autolysis of tissues. But these a priori objections, though logical, need scientific support, and I therefore arranged three series of experiments. I must I thought it own that on approaching our researches hardly probable that the blood from a dead body could be introduced with impunity into the blood system of Our notions of death suggested a whole a living animal. series of acutely toxic substances entering the blood, which must be fatal to any living organism. The first series of investigation, conducted under my direction by Dr. Kostiukov in 1927, consisted of systematic bacteriological examinations of different from animals at varying tissues and organs taken intervals after their death, and with varying conditions of storing and dead bodies. In all, 402 examinations were made of tissues and organs taken from the cadavers of 47 animals, killed in different ways and kept at a temperature of 4? to 22.5?C. at a time ranging from 15 minutes to 12 days after the death of the animal. These investigations have shown us that the development of infection in any tissue of the dead body depends upon two factors. The first is the nearness of the given tissues or organs to the chief focus of infection in healthy animals the gastro-intestinal tract, whence it, spreads rapidly by the portal system to the abdominal organs; the farther from the gut the organ the later it is infected. If there are other foci, infection from these will also proceed parallel with that from the intestine. The second factor is the temperature at which the cadaver is kept. In the most favourable conditions for preservation?about freezing point?the tissues nearest to the focus of infection begin to be infected found this in the peritoneal exudate, after 10 days. We the peritoneum itself, and the liver, while the sterility of the tissues further away from the abdominal cavity ?brain, muscles, joints, marrow, and heart blood?is preserved for 12 days and more. Even under less
754
THE INDIAN MEDICAL GAZETTE
favourable conditions these latter remain sterile at 14?C. for 60 hours, while after 24 hours at 22?C. only the bones and marrow are sterile. Consequently, we can conclude that, contrary to all supposition, the development of infection in certain organs of the dead body takes place rather late?at an appropriate temperature approximately 10 days after death?and therefore surgeons may boldly make use of material from a dead body not only some hours but even some days after death. The second series of experiments, to determine the toxicity of blood from a dead body, Dr. Kostiukov and I carried out in 1929. Appropriate experiments were made on 15 dogs with which 10 experiments were made, with different modifications. The technique of the experiments was generally as follows:? A dog was killed after measuring its weight, the blood of volume, and the haemoglobin and number erythrocytes. Then its cadaver was kept for a certain time at a temperature varying from 5? to 25?C. in different cases. At first the animals were killed with chloroform. It was possible, however, that the amount of chloroform in the blood might influence the results, so we decided to kill the animal by strangling it with the noose of a rope, death taking place almost instantly. After a period of 3 to 11 hours the body was taken into the operating-room, and under aseptic conditions paraffined glass cannulse were introduced into the central parts of the carotid and the internal jugular. By rubber tubes connected with the cannulse it was possible either to draw blood from the vessels of the cadaver or to inject solutions into them. The blood when collected was mixed with a solution of sodium citrate to avoid
coagulation. In the first experiments, when the animal was killed by chloroform and the cadaver was kept in a warm place (22?C.), it was only during the first 4 hours after death that it was possible to get enough blood. After this there was so much clotting that liquid blood could only be obtained with great difficulty after squeezing out each clot. Five hours after death it was impossible to collect blood from the vessels at all. When later proceeded to killing the animals by strangling, the
we
blood was the typical dark fluid of asphyxia, and thrombosis did not take place in it for over 10 hours, especially when the cadaver was kept in a cool place. When the blood had been thus obtained a live dog was brought into the operating-room whose blood volume, haemoglobin content, and red cell count had been determined. After exposing the deep vessels in the neck paraffined cannulse were introduced into its carotid and the internal jugular. Through the first, blood was drained from the animal and collected in a graduated cylinder; through the second, as soon as necessary, there was injected a salt solution or blood taken from the dead body. In our first experiments we made very careful and comparatively small transfusions (200 to 300 c.cm.) from the cadaver into the live dog, which had already been subjected to a moderate bleeding, not exceeding 25 per cent of its total quantity of blood. The animals seemed so well after transfusion, however, and there was such an entire absence of toxic symptoms, that we soon proceeded to more copious bleedings and to increasing the dose of the transfusion. Thus we convinced ourselves that even when we substituted blood from the cadavers for as much as 60 per cent of the total volume the animals stood the operation well without showing any sign of poisoning. It must first be mentioned that in these experiments we did not keep the cadaver in a cool place deliberately, but left it at a temperature of 17.5?C., and even 22.5?C.; and secondly, the blood was removed after the maximum time possible for such temperatures?i.e., after 4 to 5 hours, when clotting had already begun? so that before the transfusion we had to filter off a large number of clots. From these experiments, therefore, we could conclude that even when keeping the cadaver at the most unfavourable temperatures, and for the longest possible _
[Dec.,
time, the blood possesses transfused with impunity, living animals. Vitality It
no
1937
great toxicity and may be in large quantities, into
even
of cadaver blood
attempt to answer the next erythrocytes could live and function after their transplantation into a living animal. The observations in the preceding experiments already seem to give an affirmative answer to this question, since in these animals there was neither the jaundice nor the hsematuria that usually accompanies blood destruction, and their general condition was not that to be expected after the extensive bleeding that had been performed. It might be objected, however, that the blood from a dead body was simply a liquid of complex composition, which after transfusion acted purely mechanically by restoring the volume. It might also be objected that the erythrocytes of the cadaver blood were already degenerating and were thus unable to perform their functions. To settle the question, and to remove all these objections, we arranged a third series of experiments, involving a much greater loss of blood. There were 20 experiments on 35 dogs, using the same technique as that in the second series. We knew already that dogs usually die was now
possible
question, whether
to
the
when 60 to 70 per cent of the total blood volume is withdrawn. An injection of salt solution may temporarily restore the activity of the heart or of respiration, but it cannot ultimately gave the animal. Our own experiments confirmed this. After removing 70 per cent of the animal's blood, and after the immediate injection of a corresponding quantity of warmed saline, not one survived. Starting from these control figures we tried in our experiments to get the greatest possible exhaustion of blood. Since it usually ceases to flow from the carotid after 70 per cent has been withdrawn, we had to have recourse to repeated washing out of the animal's bloodvessels with warmed saline, temporarily reviving the animal. By this means we succeeded in raising the degree of blood exhaustion to 90 per cent. This is normally absolutely incompatible with life and no injections of saline or colloidal solutions can avail; only the transfusion of living, functioning blood can keep the animal alive. And yet we also succeeded in maintaining life by transfusing blood from a dead animal. The following is an example:? The dog had a total blood volume of 539 c.cm. with haemoglobin 95 per cent and red cells 6,000,000. The first bleeding removed 70 per cent of the blood, which then ceased to flow from the carotid; the heart and respiration ceased. It was revived by injecting 160 c.cm. of saline. A second bleeding from the carotid produced diluted blood containing only 29 per cent haemoglobin. Again 200 c.cm. of saline were injected and after bleeding the fluid contained only 7 per cent of haemoglobin. The total quantity of the blood withdrawn reached 90 per cent. This was again followed by_ stopping the heart and respiration. After transfusion of 450 c.cm. of blood from a dead body, taken 8 hours after death, the animal revived. On the next day the condition of the dog was good, the haemoglobin being 75 per cent, the red cells 5,700,000. The dog lived in healthy condition for several weeks and then was used for another experiment. In other experiments a similar effect was obtained by us from the transfusion of cadaver blood taken 10 and even 11 hours after the death of the animal. These experiments leave no doubt about the fact that the erythrocytes of a dead body 10 and even 11 hours after death still retain their full vitality and are able to function physiologically quite as well as the erythrocytes of normal blood. These facts were afterwards fully confirmed by the experiments of Barenboim and Skundina in 1931-32. They repeated our experiments, with various modifications, and then studied the vitality of transfused blood in dogs, using as a criterion the capability of the blood for gas exchange, which they established by Bancroft's method. Summing up the results of their experiments
Dec., 1937]
CURRENT TOPICS
upon 47 dogs, they arrive at the conclusion that for 0 and even 10 hours after death blood fully preserves its ability to fix oxygen and retains the properties of
blood from the living. To complete the picture one of my collaborators, Dr. G. G. Karavanov, in 1935 studied another of the elements of blood?the leucocytes-busing their power of phagocytosis as a criterion of their vitality. Studying this systematically during the life of the animal, and at different times after its death, he established that phagocytosis is pretty well preserved for the first 11 hours after death, after which it disappears rapidly. These data therefore are also in accordance with the facts mentioned before and confirm our fundamental thesis that the blood in a dead body preserves its vitality for about 10 hours after death, and within this period may be used for transfusion into a live organism. The experimental part of the problem of transfusing cadaver blood may therefore be regarded as decided in principle. ClilNICAL TRIAL The question now arises about the transference of this data to the transfusion of blood in man. Unfortunately a series of circumstances to do with organization prevented me from working out this part of the problem myself, and I am indebted to Professor S. S. Yudin who has continued the work that I began and has introduced into clinical practice the transfusion of blood from cadavers. The abundant material collected by him and his colleagues in the years 1932 to 1935 already includes statistical data for about 1,000 cases, and fully confirms all the fundamental principles that I have established. It was only last year that it became possible for me to use cadaver blood in my own clinical practice, and our experience in 42 cases allows me to subscribe fully to the enthusiastic support, given to this method by Professor Yudin. I must own that at first I was inclined to ascribe their enthusiasm to the zeal common to all authors of a new method. After my experimental experience I never doubted that transfusion of cadaver blood may give clinical results in no respect worse than those from using the blood of live donors. The assertion, however, that transfusions of cadaver blood sometimes give even better results than those of blood from live donors seemed to me to be wholly improbable. Nevertheless, my own clinical experience has convinced me that this fact is really true. It was shown by the quantity and quality of the reactions after transfusion. I realize that our series of 42 cases is still too small for making final conclusions, but the general impression is decidedly in favour of the fact that reactions after transfusing cadaver blood are much rarer and are much less conspicuous. For instance, in all our 42 cases a reaction was seen only six times in very seriously ill patients, principally with diseases of the hsemopoietic system. In no preceding series in our large experience?over 1,000 transfusions using citrated blood as well as the direct method?have we observed so few reactions; in fact, they used to amount to 60 and even 70 per cent. The following case illustrates the contrast between the two methods:? The patient was suffering from carcinoma in the caecum, with severe anajmia, in consequence of which he received four transfusions. At the first two he had fresh citrated blood from two donors of a corresponding group, and in both instance? the transfusion was accompanied by an extremely strong reaction, with a severe rigor, headache, collapse, and an eruption on the face. At the third transfusion he had 500 c.cm. of blood from a corpse, also of a corresponding group. This was accompanied only by a rise of temperature up to 101 ?F. There were no symptoms and his general condition was good. Once again he received fresh citrated blood from a new donor of a corresponding frroup, and this transfusion was again accompanied by a precisely similar reaction?rigor, rash, and collapse. We used an absolutelv identical method of preparing the apparatus, the salt and citrate solutions in all cases of transfusion, so as to exclude the possibility of any difference in the reactions being due to these. How can this be explained? _
755
the transfusing of cadaver blood was without our adding any anticoagulant. The fact, discovered by Skundina, that in some cases there is no coagulation, or rather on the contrary a ' disagulation' of cadaver blood, is in itself of great theoretical and practical interest, and will doubtless be Of the six cases five a great advantage for the method. had no reactions. The second great advantage of transfused cadaver blood that we have observed is that the increase of haemoglobin and red cells in the patient is higher than that usually observed after transfusions of an identical quantity of blood from live donors. The following figures show the amount of improvement in a patient with chloranaemia. She had a transfusion of 400 c.cm. of cadaver blood of the corresponding group, which had been preserved for 11 days. In six
cases
performed
Before transfusion
After transfusion
(28th May) (29th May) (10th June) Hemoglobin
Red cells White cells
33 per cent 40 per cent 53 per cent
..
..
2,300,000
..
5,200
3,000,000 5,600
4,250,000 6,200
These increases after transfusion of cadaver blood
can
only be explained by its sharp stimulation of the haemopoietic system. The action seems to be very variable, and in a number of cases we noted a much milder reaction in the blood count, as shown by a very slight leukocytosis, and by the absence of any great deviation in the Arneth count. These differences of reaction probably depend upon differences in the biological composition, which in its turn may be dependent upon the cause of death of the cadaver from which the
These questions still need further was taken. investigation. It is extremely interesting to leam that Professor V. P. Filatov, who is working on transplantation of the cornea, has arrived at a similar conclusion?that the transplanted cornea from the cadaver eye generally 'takes' better than that from a live donor (see Lancet, 1937 1, 1395). blood
Economic advantages Besides the general value of the method of transfusing cadaver blood lias also some advantages from the point of view of organization. In the first place, the dead body can be exonerated from the suspicion of disease with much greater certainty, since the most elaborate examination of a living donor is limited to clinical, serological, and radiological methods, while the postexamination may include an mortem exhaustive pathological investigation of all the organs. The other advantage is on the grounds of economy. The supply is cheap, and with an efficient organization it is possible to have always a, stock of this blood in any quantity an illustration the necessary for clinical needs. As following instance will suffice:? The cadaver was that of a man of athletic constitution, a wrestler, who had died suddenly of cerebral haemorrhage. Five hours after his death *2,800 c.cm. of blood was taken from him and received into citrate solution. Examination of the blood for syphilis and malaria gave negative results, and bacteriologically it, proved sterile. The medico-legal autopsy did not reveal after any signs of infectious disease. This blood, different periods of storing, was transfused into on the c.cm. 8th of five patients?500 day preservation to a woman with secondary anaemia; 500 c.cm. on the with a to 8th day pulmonary empyema ; 450 c.cm. patient on the 9th day to a patient with a carcinoma of the on the 11th day to another patient 400 c.cm. stomach: with empyema; and 400 c.cm. on the 11th day to a In all these cases the woman with pernicious anaemia. transfusion had the usual favourable effect. Thus the analysis of my own material leads me to the conclusion that the method of transfusing cadaver blood has a number of very definite advantages. It is true, however, that these advantages can be made use of in practice only with widespread and efficient organization for procuring the cadaver blood, _
THE INDIAN MEDICAL GAZETTE
756
[Dec.,
1937
and this is only possible in large centres. In practice the normal organization of transfusing such blood is still meeting a great many difficulties, chiefly from medico-judicial institutions. In spite of the fact that there is a large body of supporting evidence for its value and that full sanction has been obtained for taking blood from cases of sudden death with the observance of certain formalities, the medical men at the courts of justice were unwilling to allow the blood of bodies that are at their disposal to be drawn for clinical needs. Yet here, by an active co-operation with those in charge of local mortuaries, there is opportunity for a further practical development of the method of obtaining cadaver blood.
method of carrying out the treatment and presentation of twenty cases. It has long been noted that creosote, guaiacol and their derivatives have an almost specific action on the secondary infection occurring in open pulmonary tuberculosis but no beneficial effect on the tuberculous process -per se. The literature on the therapeutic value of these substances in non-tuberculous lung infections is scant and indefinite. The purpose of this sti^dy was to investigate the effects of one of these substances, guaiacol, on the course of acute and chronic nontuberculous lung abscess.
Prejudices
Guaiacol, phenol ester, was isolated in crystalline form in 1887 by Behal and Chosy. It is a colourless or yellow crystalline mass which darkens on exposure to air or light, melts at 28?C. and remains liquid for a long time even at lower temperature, boils at 20i?C., is insoluble in water and has an agreeable aromatic odour. Attempts to reduce its toxic and irritating properties by esterification have resulted in the preparation of numerous derivatives, many of which are soluble and practically innocuous. If guaiacol or any of its esters is to have any direct action on any pathologic condition in the lungs, it is reasonable to expect that it. will be excreted through them. Bufalini in 1904 reported that guaiacol, when administered orally, was not excreted through the lungs. In 1915 Hofbauer showed that, when injected hypodermically, guaiacol was found to be present in large amounts in the blood, liver and spleen and somewhat less in the lungs and kidneys. It is evident then that, in order to reach the lungs, guaiacol or any of its esters must be introduced by either the hypodermic or the
There is a strong prejudice in the majority of people at the bare thought of transfusing into a live person the blood from a corpse. One need not, however, go very deeply into these subconscious prejudices to understand that they are of the same order as the primitive instincts that had to be overcome in the early days of ordinary blood transfusion. There is yet another objection put forth by the patient and his relatives. Cadaver blood in the imagination of a simple and narrow-minded person is ' involuntarily connected with ptomaines', corruption, a multitude of microbes, and with the idea that the one to whom this blood has belonged has ceased to exist, and is now exposed to the horrible process of putrefaction. It will be seen therefore that all these notions are thoroughly unscientific, and are associated with the tendency to impart- to the blood a whole with the of mystic properties connected series personality of its former host. This conception is also illogical, since in medicine there is now a wide use for blood taken from slaughter-houses, as well as for different organs, prepared in different ways and injected into the veins of a patient. Everyone has become accustomed to this, and nobody protests against it. How much more simple and natural, then, it is to use instead of the blood of a dead animal the blood of a dead human being? Surely after a certain period man will overcome these prejudices as easily as the numerous others that have arisen during the history of the development of blood transfusion. Conclusions The transfusion of cadaver blood
seems
to be funda-
mentally established, experimentally as well as clinically. The method is not only equal to other methods of transfusion, applied in clinics, but may even have some advantages over them. Further advances may be made along the following lines; first, by a more detailed study of the biochemical changes in the blood after its death; secondly, by accumulating further clinical observations; and thirdly, by an efficient organization that will make use of the many
opportunities
Chemical
investigation
a
to collect blood
from all suitable
cadavers.
The Treatment of Lung Abscess by Means of Guaiacol Intravenously. An Analysis of Twenty Cases By C. H. NAMMACK,
m.d.
and A. M. TIBER, m.d. (Abstracted from the Journal of the American Medical Association, Vol. CIX, 31st July, 1937, p. 330) The use of guaiacol intravenously in the treatment of lung abscess was begun in the Fourth Medical Division of Bellevue Hospital in 1922. The results obtained in the early cases were sufficiently encouraging to decide us to make a more analytic study of this method of treatment. In all about fifty cases have been so treated. This article deals with the procedure and
intravenous route. Because solutions of guaiacol or its esters are somewhat irritating when given hypodermically, intravenous injections are preferred. Thus, the only derivatives of guaiacol that can be used in this study must be readily soluble in water. Of the water-soluble derivatives, potassium guaiacol sulphonate and calcium guaiacol sulphonate are the most readily available and have been used most extensively. However, these esters are inactive and must be saponified into their constituents and the active principle, guaiacol, liberated. When an aqueous solution of either of these compounds is administered intravenously, guaiacol can be recovered in the sputum, but the amount recovered is very small compared with the amount actually injected. It is evident then that, in order to obtain a large amount of guaiacol in the sputum, free guaiacol should be injected intravenously. However, guaiacol is insoluble in water; but if from 5 to 10 grains (0.3 to 0.65 gm.) of pure guaiacol is dissolved in from 1 to 2 c.c. of 95 per cent ethyl alcohol the guaiacol can be dissolved in an aqueous solution containing 2i grains (0.16 gm.) of sodium iodide. If either the iodide or the guaiacol is increased in amount, the guaiacol is precipitated out and can "be redissolved only by the addition of more alcohol. A solution of from 5 to 10 grains of guaiacol, 2 c.c. of ethyl alcohol and 18 c.c. of water containing 2J grains of sodium iodide is stable and will keep in a dark container for a number of months before the guaiacol will precipitate out. This solution was prepared for us by various companies and is the solution that gave the best results. This solution is somewhat irritating to the subcutaneous tissues and should be injected only after the blood has welled into the syringe. Pulmonary excretion op guaiacol The sputums of patients with definite lung abscesses were collected for three consecutive twenty-four-hour periods. Each sample was measured, acidified and distilled with steam and the distillate was collected in 20 c.c. portions. Each portion was tested with Millon's reagent for the presence of free phenol and if free phenol was found only in the first 20 c.c. of the distillate, it was termed one plus; if in the first and second,
CURRENT TOPICS
Dec., 1937J
two plus; if in the first, second and third, three plus, and in all four, four plus. The same procedure was followed after each patient was given an intravenous injection of 20 c.c. of guaiacol solution. When a solution 'containing free guaiacol is given intravenously to patients with, lung abscesses, their sputurns for from forty-eight to seventy-two hours after the injection contain a substance which gives a positive reaction with Millon's reagent. In view of the fact that no phenol bodies were present in the sputums of these patients for four consecutive days prior to the intravenous administration of guaiacol, it is reasonable to assume that the phenol body present in the sputum after the injection is guaiacol or a derivative of it.
While these experiments were being conducted, a patient with a putrid lung abscess was operated on in It was deemed our surgical division (thoracotomy). wise to examine chemically the drainage from the lung for the presence of volatile phenols. The drainage was collected for two consecutive days and the dressings and drainage distilled with steam. The distillate was collected in 20 c.c. portions as described previously and each portion tested with Millon's reagent. The patient was then given an intravenous injection of 20 c.c. of the guaiacol and iodide solution and the drainage and dressing for the next seventy-two hours collected and treated as before. The drainage from the lung abscess cavity contained no volatile phenol bodies; but, following the intravenous administration of the guaiacol solution, the drainage from the abscess cavity contained a volatile phenol which gave a positive reaction with Millon's reagent. It is evident, then, that when guaiacol .is injected intravenously it is excreted through the lungs of patients with lung abscesses as a volatile phenol body.
Summary of
treated cases with two- to five-year folloiv up Total Cured Deaths
Cases Duration of symptoms Less than 3 months (acute) More than months 3 ..
(chronic) Site of abscesses Solitary R. U. L. R. M. L. R. L. L. L. U. L. L. L. L.
..
..
..
..
..
..
..
..
..
4
S
8
0
12
8
4
10 0 2
9 0 2 3 2
1
..
..4
..
..
Multiple
..
Non-alcoholic
..
..
..
2
..1
R. U. L., L. L. L. L. IT. L.. L. L. L. Alcoholic Condition of gums and teeth
1 10 10
..
5
..
15 ..11
..
4
Healthy Suppurative gingivitis Treated (11) Untreated (4) Age distribution 20-29 years (3rd decade) 30-39 years (4th decade) 40-49 years (5th decade) 50-59 years (6th decade) Sex Male Female
16
20
..
..
v
0 0 ..
..
1
1 1 2 2
..
10. On discharge the patient was sent to a convalescent home and not permitted to resume work until the
roentgenograms revealed complete healing. The summarized results of twenty treated shown in the table above.
Comment The results have been satisfactory and it is noteworthy that Unger using an injectionable guaiacol solution obtained similar results at the Rudolf Virchow Hospital in Berlin. In the present study of twenty treated cases, it was found that the patients felt considerably better in a very short time, owing to the subsidence of the fever and cough and to the decrease of the daily sputum output and the loss of its foul odour. Serial roentgenograms showed early regression of the large area of pneumonitis surrounding the abscess cavity and later its actual disappearance. It is felt that the eradication of all foci of infection about the mouth, nose and throat and moderate restriction of all activities until the roentgenogram shows complete healing is very essential if the results of this type of treatment are to be permanent. Of the four deaths in this series, one was due to a malignant condition of the lung, one to traumatic subdural haunorrhage, and two to recurrence of the abscess. It is well to point out that the abscess reappeared in those patients who refused to have their infected gums treated. Because many lung abscesses heal spontaneously and because of the danger of early operation, most authorities agree that acute lung abscesses should be treated medically from six to twelve weeks before any surgical procedures are resorted to. Yet, after reviewing the literature, one is impressed with the lack of active medical treatment during this period. As the intravenous use of guaiacol causes early subsidence of the symptoms and a regression of the pathologic condition in the lung without producing any unfavourable reactions, it appears that this type of therapy should be used in the treatment of patients with acute and chronic lung abscess.
Use of
Prostigmin as a Diagnostic Myasthenia Gravis
17 3
Test of
m.d.
H. SCHEIE 4
(From the Journal of the American Medical Association Vol. CIX, 7th August, 1937, p. 413)
..
2
That prostigmin relieves the muscular weakness of myasthenia gravis has now been accepted quite generally
..
2
..
..
2 2
Treatment The following routine was adopted for the treatment of patients with acute or chronic lung abscesses:? 1. Bed rest if the rectal temperature was above 99.8 ?F. 2. Twenty-four-hour collection of sputum. 3. Temperature taken every four hours.
'
by all observers who have studied the drug. The relief furthermore, has provided new insight into the mechanisms at fault in the disease.
..
cases are
11 0
8
4
improved.
and
1
7
4. X-ray films of chest, in postero-anterior, lateral and oblique positions; repeated every three to four weeks. 5. Examination of teeth and careful mouth hygiene and extraction of decayed teeth if necessary. 6. Bronchoscopy soon after admission. 7. No tobacco or alcoholic drinks. 8. High caloric diet. 9. Intravenous injection of guaiacol every third or fourth day. All patients were given the solution until the amount of the sputum was reduced, its foul odour disappeared and the general condition of the patient
By G. D. GAMMON, 5
..
..
757
The
possibility
of
using the response to prostigmin as a diagnostic test of myasthenia has not, however, been fully appreciated It is true that Viets and Schwab have found that the weakness due to lesions of the central and peripheral nervous system was not materially improved. However the effect of prostigmin on the muscular diseases has not been systematically studied. We have accordinglv examined the action of the drug on the weakness due to a variety of diseases of the muscular system None of the patients obtained any striking' relief from
758
THE INDIAN MEDICAL GAZETTE
prostigmin. Therefore myasthenia gravis is the
only
condition examined thus far in which muscular weakness is consistently and markedly improved. For this reason it seems fair to conclude that a response to prostigmin may be used as a diagnostic test of the disease. Material and methods The
studied include four cases of myasthenia of which hyperthyroidism had developed; five cases of progressive muscular dystrophy ; two cases of myotonic dystrophy; one case of family periodic paralysis; two cases of amyotonia congenita; five normal adults, and three normal children. The patients were studied in the Neurological, Medical and Pediatric services of the University Hospital; diagnoses were made after careful study. In estimating changes in muscular contraction we observed facial movements and, wherever possible, we employed such objective tests as weight lifting, dynamometer tests and the height to which a mercury column could be blown. In some cases myographic records were made. As a test dose from 1.5 to 2 mg. of prostigmin hypodermically was used, combined with atropine sulphate 1/100 grain (0.00065 gm.). It should be emphasized that a large dose is required to obtain the desired response. Children tolerate about half the adult dose. cases
gravis, in
Effects
one
of
prostigmin
in
cases
of
muscular
disease
AND MYASTHENIA AND IN NORMAL PERSONS
Prostigmin in doses ordinarily employed in the treatmyasthenia sets up marked fibrillary tremors
ment of
in the muscles of normal persons and in all these cases of muscular disease except myasthenia. While best seen in the eyelids and tongue, the fibrillations occurred irregularly throughout the body and did not selectively affect the diseased muscle. The twitching probably
1937
[Dec.,
results from repetitive contraction of small groups of fibres in response to tonic impulses, since Brown, Dale and Feldberg have observed that muscle treated with _
physostigmine gives
a
multiple
response
to
a
single
stimulus applied to the motor nerve. In the muscular dystrophies the twitching was considerably more marked than in normal persons, indicating probably an increased sensitivity to the drug. In myasthenia gravis, in contrast to these cases, fibrillations almost never occurred; only rarely were they observed in the lids. The absence of a normal reaction suggests that the myasthenic process is generalized and widespread. While the lack of fibrillary twitching distinguished myasthenia from the other cases examined, a much For the weakness more striking difference was evident. of myasthenia was consistently and spectacularly relieved, but that of the other conditions was either not materially affected or, in some cases, was slightly increased. Thus only one of the seven patients with dystrophy obtained an increase in strength and this careful measurement to was so slight as to require demonstrate the change. The patient with periodic family paralysis was made somewhat weaker. Thus, of the various muscular diseases that we examined, myasthenia gravis alone responded to prostigmin with significant increase in the strength of muscular contractions. Since, then, others have shown that weakness due to lesions in the central and peripheral nervous systems is also not materially improved by prostigmin, a marked improvement in muscular weakness by prostigmin and the absence^ of fibrillary tremors is a diagnostic test of myasthenia. In other words, prostigmin appears specific for myasthenic weakness, since it relieves no other condition so far examined. It is possible that prostigmin may find its_ widest usefulness as a test to differentiate myasthenia from other causes of muscular weakness.
Topics patient should begin with a daily dose of 10 g. of succinic acid, that this dosage should be maintained until 1 or 2 days after disappearance of the acetonuria, and that it should then be gradually reduced. The acid is given after meals as a 2 per cent solution in tapwater, the total dose being divided throughout the day. Unfortunately it is apt to produce severe nausea, and causes distress especially to patients with hyperacidity, so that experiments are now being made with its administration in capsules, or as the calcium salt in powder form. Szent-Gyorgyi provides an explanation of these findings in terms of tissue metabolism. During the last few years he has developed a theory that the respiration of tissues is catalyzed by certain C4-dicarboxylic acids, of which succinic acid is one. He now claims that in particular the oxidation of pyruvic acid, an intermediary substance in the metabolism of carbohydrates, is catalyzed by these C4 acids. He further states that if for any reason this catalysis fails, the pyruvic acid is not oxidized, but is instead converted into acetone bodies. (That such a conversion can occur has indeed been known for many years.) He therefore suggests that the ketosis of diabetes is due to failure of the C4 acids to catalyze the oxidation of pyruvic acid, this failure probably being due to a shortage of C4-dicarboxylic acids in diabetes, either because their formation is inhibited or because their destruction is accelerated. Administration of small amounts of a C4-acid, such as succinic acid, might thus, it is argued, restore catalysis of the pyruvic acid oxidation and so stop the formation of acetone bodies. Whether this argument will prove acceptable cannot be decided before publication of the evidence on which it rests. From the clinical standpoint, however, it is clear that if others have the same experiences as Koranyi and SzentGyorgyi a substantial advance will have been made in improving the lot of the diabetic. Succinic acid is cheap, and the advantage of its being given by mouth needs no emphasis. If the dose of insulin can be new
A New
Remedy
for Diabetic Ketosis
(From the Lancet, 24th July, 1937, Vol. II, p. 200) Professor Szent-Gyorgyi's record as an investigator immediate attention for his latest and most exciting observations. In brief, an idea springing from his studies of tissue metabolism led him to try the effect of succinic acid as a remedy for the ketosis of diabetes. Only five patients have so far been treated, but in one of these it was found that as little as 1.0 gramme daily by mouth would remove ketosis, the acetone bodies disappearing completely from the urine and the alkali reserve rising. In one of these cases the patient had suffered from diabetes for several years and had been kept free from ketonuria and glycosuria by a carefully controlled diet and 70 units of insulin daily. But even this treatment had failed in the long run, and just before her treatment with succinic acid her symptoms were severe, with a blood-sugar of 352 mg. per 100 c.cm., and an alkali reserve of 25 vols, per cent. Koranyi and Szent-Gyorgyi discontinued the insulin injections, and gave instead 10 g. of succinic acid per day orally. By the fourth day, though the concentration of sugar in the urine was unaltered, acetone bodies had disappeared from the urine, and later the alkali reserve That this remarkable was found to have risen sharply. result was not merely fortuitous was shown on two occasions by return of ketosis when use of the acid was stopped for a few days. Finally it proved possible to reduce the dose of succinic acid to 1.0 g. per day, and at the same time the urine could be kept sugar-free by the simultaneous administration of 10 units of insulin daily?in contrast to the 70 units previously given. Though this was the most striking of the five cases the others also yielded evidence of the antiketogenic effect of the acid. In announcing these results at an early stage Koranyi and Szent-Gyorgyi wish the possibilities of their method to be explored by others. From their brief experience they suggest that the treatment of a ensures
752
THE INDIAN MEDICAL GAZETTE
reduced when succinic acid is given at the same time, a great saving will be effected; and the use of one of the new combinations of insulin with a prolonged action might mean that the dosage could be kept at a very low level indeed.
Nutritional Needs in Pregnancy * By Sir ROBERT McCARRISON,
m.d., f.r.c.f.
(Retd.) (From the British Medical Journal, 7th August, 1937, Vol. II, p. 256) Last year at the inaugural meeting of the Section of Nutrition in Oxford, I ventured to predict that the day was not far distant when, instead of one morning being devoted to its work, it would rank with the Section of Medicine as a three-day fixture. To-day my prediction MAJOR-GENERAL, I.M.S.
is two-thirds of the way towards fulfilment. And it is perhaps fitting that the Section of Obstetrics and Gynaecology should be the first to ally itself with that of Nutrition. By this alliance and by the application of the principles of nutrition to the mothers of our race and to their children we begin at the beginning to lay the foundations of a more healthful existence for our people?a finer structure of national' health. For, as Carrell has recently reminded us, nutrition is synonymous with existence'; synonymous, that is to say, with the act of living, with the exercise of the vital functions. To this I would add that faulty nutrition is synonymous with faulty existence, with the faulty exercise of the vital functions. For the student of nutrition there is no more enlightening experience than to observe the behaviour of cells under cultural conditions in vitro. Soon lie perceives that their growth, their reproduction, their structure, and their functions depend not only on the composition of the fluid medium in which they are immersed but on the removal from it of the waste products of their activities. So it is with the human body; that vast aggregation of cells, living, moving, and having their being within the closed circuit of the blood stream. For them the continual purification of the fluid medium in which they live is as necessary to their well-being as its continual enrichment with essential nutrients. It is to these two ends that the processes involved in the function of nutrition are directed and co-ordinated. Inspiration, mastication, deglutition, digestion, absorption, and circulation; these are the supply services. Exhalation, perspiration, urinary excretion, and defalcation: these are the sanitary services. The central act?assimilation?in the series of processes involved in nutrition is a function of living matter, dependent on the efficiency of the supply services on the one hand and on that of the sanitary services on the other. To the cell belongs the task of nourishing itself; to us, as physicians, belongs the task of enabling it to do so by our supervision of the efficiency of these two services. Nutrition, then, is the sum of the acts or processes by which the structure and functions of all organs and parts of the body?including, of course, those that subserve the function of reproduction?are established and maintained. It is, in short, that function of the body by which health is maintained: health, which implies the ability to produce and rear offspring fitted to live and efficiently to perform the functions of their species. Continued efficiency of the function of nutrition It is customary to speak of nutrition in pregnancy as though it differed in some directions?in the supply of certain food essentials, for instance?from nutrition of other periods of life. Indeed, the very title of our subject suggests such a distinction. It is customary also to speak of pregnancy as though it involved an additional burden on the maternal organism, as, unfortunately, it often does. But I suggest to you that the * Read in opening a discussion at a joint, meeting of ihe Sections of Nutrition and Obstetrics and Gynaecology at the Annual Meeting of the British Medical Association, Belfast, 1937.
[Dec.,
1937
nutritional needs in pregnancy are those necessary to the continued efficiency of the function of nutrition throughout life. For in this efficiency the efficiency of that other fundamental function of the body?reproduction ?is inherent. As well might we regard the taking of a steep hill as a feat additional to the normal function of a motor car as regard the making of a seven-pound baby as a feat additional to the normal function of woman. The properly constructed car, the properly adjusted, oiled, greased, fuelled, and tended car takes the hill in its stride; the properly constructed, adjusted, fuelled, and tended woman takes pregnancy in hers. It is this construction, this adjusting, this fuelling, this tending, that, in the perfection of its operation, the function of nutrition effects. But the case is different with the ill-constructed, the ill-adjusted, the ill-tended woman, in whom the function of nutrition from infancy onwards has been faulty. Then, indeed, pregnancy becomes a feat to which some succumb and from which many emerge with some weakness exposed, some permanent damage incurred. It is not, however, with the ill-constructed, the ill-adjusted, the ill-nourished, the ill-conditioned that I am here concerned, but with the Rolls-Royce of womanhood, or for that matter with the dependable Baby Austin or Morris Minor. It is to the production of these?aye, to their mass-production? that we must direct our energies, though the salvaging, the patching-up, of wrecks must still remain our portion. The nutritional needs in pregnancy are, I repeat, those necessary to the efficiency of the function of nutrition. Their satisfaction must begin not with conception but with the antenatal life of the mothers of our race. It must continue throughout the period of their growth and development up to, during, and following the period when they find their fulfilment in motherhood: a fulfilment for which nutrition prepares and makes ready the way?sometimes well, sometimes ill, according to its perfection or imperfection. It is impossible to dissociate reproduction from nutrition. It is impossible to dissociate reproduction from the acts and processes involved in nutrition. Respiration, digestion, absorption, secretion, circulation, assimilation, excretion: these are prologues to the crowning act of the imperial theme of motherhood. Four
things
needful
the things needful to the efficiency of the function of nutrition? They are: First, the adequate provision of the materials with which this function is effected: oxygen, water, properly constituted food, and a substance or substances produced in the skin by the action of sunlight. Second, the efficient performance of each one of the acts or processes involved in nutrition, these acts or processes being themselves dependent on the proper nourishment of the organs and tissues performing them. Third, the practice of measures and habits of life favourable to the efficiency of the function of nutrition: appropriate exercise in the open air, proper breathing, agreeable mental occupation, promotion of the function of the skin by bathing, suitable clothing, and exposure of parts of the body to such sunlight as is available, promotion of the action of the kidneys and bowels by proper food and the free consumption of water. Fourth, the avoidance of all influences that adversely affect the function of nutrition: such, for instance, as insufficient rest and want of sleep, bad ventilation, insanitary conditions generally, worry, emotional excitement, constipation, alcohol, and infection. These are the nutritional needs in pregnancy as they are the nutritional needs of the body throughout life. Their satisfaction makes of pregnancy one of the happiest, the most healthful, periods of a woman's life.
What, then,
are
Dietetic requirements in pregnancy This brings me to that section of our subject which, to judge by the programme before us, is to occupy the remainder of this morning's session: dietetic requirements in pregnancy. I shall not attempt to discuss these requirements in detail, but will content myself with an enumeration of the foodstuffs which, if properly
CURRENT TOPICS
Dec., 1937]
and properly combined, provide all the food essentials the prospective mother needs. These foodstuffs are, in order of precedence: (1) Milk and the products of milk (butter, cheese, skimmed milk, buttermilk). (2) Whole or lightly milled cereal grains; in particular a good wholemeal bread or standard bread, and oatmeal. (3) Green and leafy vegetables. (4) Root vegetables, particularly potatoes, carrots, and onions. (5) Fruit, including the tomato. (6) Pulses. (7) Egg. (8) Meat, including fish, fowl, and glandular organs. To these there must in this country be added cod-liver oil, not in the large doses commonly prescribed but in the sufficient dose of a teaspoonful daily. And as an additional assurance of functional efficienc}' of blood, muscle, and nerve, a portion of yeast extract is a wise precaution. Those of you who have studied the revised report of the Technical Commission appointed by the League of Nations to define the nutritional needs of the human being in the course of development from conception to adult age will be aware that it is from these foodstuffs that the Commission prepared their dietary schedules for all periods of life up to and including pregnancy. They had in mind, no doubt, the preparation of the female of the human species for motherhood.
produced, properly treated,
Animal protein: wholemeal bread One revision of this report has been made, and 1 hope that the next one, already foreshadowed, will remove what, in my opinion, are three blemishes on its excellence. The first of these is the unnecessarily high amount of animal protein (68 grammes out of a total protein content of 105 grammes) it prescribes. The 40 grammes provided by milk and cheese are sufficient? though an additional 10 grammes may be provided by liver, fish, or meat?sufficient, that is to say, if whole cereal or lightly milled cereals be used instead of highly milled ones and if more green-leaf vegetables be included in the diet. Phj'siological as well as economic prudence forbids a greater intake of animal protein than is needful. My second criticism is the insufficient insistence on the use of wholemeal bread. ' White flour in the process of milling is deprived of important nutritive elements. Its use should be decreased and partial substitution by lightly milled cereals, and especially potatoes, is recommended'. The exhortation is well enough so far as it goes. But it is complete, not partial, substitution that must, in my view, be at all times and in all places insisted upon. For the important nutritive elements of which white flour is deprived include the_ vitamin-B complex, vitamin E, an unidentified hemopoietic factor, the proteins of the germ and bran which are of relatively high nutritive value and so constituted as to supplement those of the interior of the grain, and fibre, which is of particular merit in ensuring the efficient action of the bowels. It is folly to deprive bread?the staff of life?of nutritive elements so important to the well-being of the body, whether in pregnancy or at other periods of life.
/
Fresh vegetables and fruit The third criticism that I have to offer is the relative paucity of fresh green vegetables and raw ripe fruit in the dietary schedule. These should form a large part of the daily diet. It is not alone for their vitamin-C content that they are of such value, but for their proteins which, though small in amount, are of high biological value, for their mineral contents, and for their utility in maintaining the balance between alkaliyielding and ingredients of the food.
acid-yielding
The Transfusion of Stored Cadaver Blood By Professor W. N. SHAMOV (From the Lancet, 7th August, 1937, Vol. II, p. 30G) It is well known that the death of
an
animal by
no
means involves a simultaneous death of all its tissues and organs. For instance, the muscles removed from
the body of
a
recently killed animal remain contractile
^
for several hours; other examples include the heart, the the endocrine blood-vessels, and glands. Death therefore, is only the moment of destruction of an intricate complex of connections and mutual relations between the separate tissues of an organism, which retain their full vitality and function for a varying time. The time depends chiefly on how far the artificial conditions are able to satisfy their fundamental requirements of nutrition and the removal of the products of metabolism. The most elementary of these conditions are shown by tissiie cultures, which may grow in vitro for an unlimited time so long as they are periodically washed and transplanted on new nutritive media. But the vitality of such organs as the heart requires for its support a very much more complicated environment which it is difficult to create artificially, and they can exist in vitro for only a comparatively short time. The ideal conditions, of course, would be found only in another living organism where all the processes of nutrition and metabolism are accurately regulated. A good example of this is given by blood transfusion, where the blood of one animal after long preservation in vitro can be successfully transfused into another, and continue to accomplish all its fundamental functions. From this an extremely interesting question arises: Could not some tissues or organs from the dead body be transferred to the living and continue to function normally? Can a defect in a living body be remedied by the transplantation of tissue from the dead, already doomed soon to perish? The solution of this problem would not only be of the greatest biological interest but might also disclose wide prospects for practical surgery. Preliminary
experiments
As the object of my first researches in this direction I selected the blood, since more is known about the method of its transference, and all the destructive processes that develop after death have a greater influence on it than is the case in any other tissue. Against this there is the weighty objection that an abundant bacterial flora may enter the blood stream even during the last agony, and that, moreover, it must contain a great quantity of toxic substances as the result of death and the autolysis of tissues. But these a priori objections, though logical, need scientific support, and I therefore arranged three series of experiments. I must I thought it own that on approaching our researches hardly probable that the blood from a dead body could be introduced with impunity into the blood system of Our notions of death suggested a whole a living animal. series of acutely toxic substances entering the blood, which must be fatal to any living organism. The first series of investigation, conducted under my direction by Dr. Kostiukov in 1927, consisted of systematic bacteriological examinations of different from animals at varying tissues and organs taken intervals after their death, and with varying conditions of storing and dead bodies. In all, 402 examinations were made of tissues and organs taken from the cadavers of 47 animals, killed in different ways and kept at a temperature of 4? to 22.5?C. at a time ranging from 15 minutes to 12 days after the death of the animal. These investigations have shown us that the development of infection in any tissue of the dead body depends upon two factors. The first is the nearness of the given tissues or organs to the chief focus of infection in healthy animals the gastro-intestinal tract, whence it, spreads rapidly by the portal system to the abdominal organs; the farther from the gut the organ the later it is infected. If there are other foci, infection from these will also proceed parallel with that from the intestine. The second factor is the temperature at which the cadaver is kept. In the most favourable conditions for preservation?about freezing point?the tissues nearest to the focus of infection begin to be infected found this in the peritoneal exudate, after 10 days. We the peritoneum itself, and the liver, while the sterility of the tissues further away from the abdominal cavity ?brain, muscles, joints, marrow, and heart blood?is preserved for 12 days and more. Even under less
754
THE INDIAN MEDICAL GAZETTE
favourable conditions these latter remain sterile at 14?C. for 60 hours, while after 24 hours at 22?C. only the bones and marrow are sterile. Consequently, we can conclude that, contrary to all supposition, the development of infection in certain organs of the dead body takes place rather late?at an appropriate temperature approximately 10 days after death?and therefore surgeons may boldly make use of material from a dead body not only some hours but even some days after death. The second series of experiments, to determine the toxicity of blood from a dead body, Dr. Kostiukov and I carried out in 1929. Appropriate experiments were made on 15 dogs with which 10 experiments were made, with different modifications. The technique of the experiments was generally as follows:? A dog was killed after measuring its weight, the blood of volume, and the haemoglobin and number erythrocytes. Then its cadaver was kept for a certain time at a temperature varying from 5? to 25?C. in different cases. At first the animals were killed with chloroform. It was possible, however, that the amount of chloroform in the blood might influence the results, so we decided to kill the animal by strangling it with the noose of a rope, death taking place almost instantly. After a period of 3 to 11 hours the body was taken into the operating-room, and under aseptic conditions paraffined glass cannulse were introduced into the central parts of the carotid and the internal jugular. By rubber tubes connected with the cannulse it was possible either to draw blood from the vessels of the cadaver or to inject solutions into them. The blood when collected was mixed with a solution of sodium citrate to avoid
coagulation. In the first experiments, when the animal was killed by chloroform and the cadaver was kept in a warm place (22?C.), it was only during the first 4 hours after death that it was possible to get enough blood. After this there was so much clotting that liquid blood could only be obtained with great difficulty after squeezing out each clot. Five hours after death it was impossible to collect blood from the vessels at all. When later proceeded to killing the animals by strangling, the
we
blood was the typical dark fluid of asphyxia, and thrombosis did not take place in it for over 10 hours, especially when the cadaver was kept in a cool place. When the blood had been thus obtained a live dog was brought into the operating-room whose blood volume, haemoglobin content, and red cell count had been determined. After exposing the deep vessels in the neck paraffined cannulse were introduced into its carotid and the internal jugular. Through the first, blood was drained from the animal and collected in a graduated cylinder; through the second, as soon as necessary, there was injected a salt solution or blood taken from the dead body. In our first experiments we made very careful and comparatively small transfusions (200 to 300 c.cm.) from the cadaver into the live dog, which had already been subjected to a moderate bleeding, not exceeding 25 per cent of its total quantity of blood. The animals seemed so well after transfusion, however, and there was such an entire absence of toxic symptoms, that we soon proceeded to more copious bleedings and to increasing the dose of the transfusion. Thus we convinced ourselves that even when we substituted blood from the cadavers for as much as 60 per cent of the total volume the animals stood the operation well without showing any sign of poisoning. It must first be mentioned that in these experiments we did not keep the cadaver in a cool place deliberately, but left it at a temperature of 17.5?C., and even 22.5?C.; and secondly, the blood was removed after the maximum time possible for such temperatures?i.e., after 4 to 5 hours, when clotting had already begun? so that before the transfusion we had to filter off a large number of clots. From these experiments, therefore, we could conclude that even when keeping the cadaver at the most unfavourable temperatures, and for the longest possible _
[Dec.,
time, the blood possesses transfused with impunity, living animals. Vitality It
no
1937
great toxicity and may be in large quantities, into
even
of cadaver blood
attempt to answer the next erythrocytes could live and function after their transplantation into a living animal. The observations in the preceding experiments already seem to give an affirmative answer to this question, since in these animals there was neither the jaundice nor the hsematuria that usually accompanies blood destruction, and their general condition was not that to be expected after the extensive bleeding that had been performed. It might be objected, however, that the blood from a dead body was simply a liquid of complex composition, which after transfusion acted purely mechanically by restoring the volume. It might also be objected that the erythrocytes of the cadaver blood were already degenerating and were thus unable to perform their functions. To settle the question, and to remove all these objections, we arranged a third series of experiments, involving a much greater loss of blood. There were 20 experiments on 35 dogs, using the same technique as that in the second series. We knew already that dogs usually die was now
possible
question, whether
to
the
when 60 to 70 per cent of the total blood volume is withdrawn. An injection of salt solution may temporarily restore the activity of the heart or of respiration, but it cannot ultimately gave the animal. Our own experiments confirmed this. After removing 70 per cent of the animal's blood, and after the immediate injection of a corresponding quantity of warmed saline, not one survived. Starting from these control figures we tried in our experiments to get the greatest possible exhaustion of blood. Since it usually ceases to flow from the carotid after 70 per cent has been withdrawn, we had to have recourse to repeated washing out of the animal's bloodvessels with warmed saline, temporarily reviving the animal. By this means we succeeded in raising the degree of blood exhaustion to 90 per cent. This is normally absolutely incompatible with life and no injections of saline or colloidal solutions can avail; only the transfusion of living, functioning blood can keep the animal alive. And yet we also succeeded in maintaining life by transfusing blood from a dead animal. The following is an example:? The dog had a total blood volume of 539 c.cm. with haemoglobin 95 per cent and red cells 6,000,000. The first bleeding removed 70 per cent of the blood, which then ceased to flow from the carotid; the heart and respiration ceased. It was revived by injecting 160 c.cm. of saline. A second bleeding from the carotid produced diluted blood containing only 29 per cent haemoglobin. Again 200 c.cm. of saline were injected and after bleeding the fluid contained only 7 per cent of haemoglobin. The total quantity of the blood withdrawn reached 90 per cent. This was again followed by_ stopping the heart and respiration. After transfusion of 450 c.cm. of blood from a dead body, taken 8 hours after death, the animal revived. On the next day the condition of the dog was good, the haemoglobin being 75 per cent, the red cells 5,700,000. The dog lived in healthy condition for several weeks and then was used for another experiment. In other experiments a similar effect was obtained by us from the transfusion of cadaver blood taken 10 and even 11 hours after the death of the animal. These experiments leave no doubt about the fact that the erythrocytes of a dead body 10 and even 11 hours after death still retain their full vitality and are able to function physiologically quite as well as the erythrocytes of normal blood. These facts were afterwards fully confirmed by the experiments of Barenboim and Skundina in 1931-32. They repeated our experiments, with various modifications, and then studied the vitality of transfused blood in dogs, using as a criterion the capability of the blood for gas exchange, which they established by Bancroft's method. Summing up the results of their experiments
Dec., 1937]
CURRENT TOPICS
upon 47 dogs, they arrive at the conclusion that for 0 and even 10 hours after death blood fully preserves its ability to fix oxygen and retains the properties of
blood from the living. To complete the picture one of my collaborators, Dr. G. G. Karavanov, in 1935 studied another of the elements of blood?the leucocytes-busing their power of phagocytosis as a criterion of their vitality. Studying this systematically during the life of the animal, and at different times after its death, he established that phagocytosis is pretty well preserved for the first 11 hours after death, after which it disappears rapidly. These data therefore are also in accordance with the facts mentioned before and confirm our fundamental thesis that the blood in a dead body preserves its vitality for about 10 hours after death, and within this period may be used for transfusion into a live organism. The experimental part of the problem of transfusing cadaver blood may therefore be regarded as decided in principle. ClilNICAL TRIAL The question now arises about the transference of this data to the transfusion of blood in man. Unfortunately a series of circumstances to do with organization prevented me from working out this part of the problem myself, and I am indebted to Professor S. S. Yudin who has continued the work that I began and has introduced into clinical practice the transfusion of blood from cadavers. The abundant material collected by him and his colleagues in the years 1932 to 1935 already includes statistical data for about 1,000 cases, and fully confirms all the fundamental principles that I have established. It was only last year that it became possible for me to use cadaver blood in my own clinical practice, and our experience in 42 cases allows me to subscribe fully to the enthusiastic support, given to this method by Professor Yudin. I must own that at first I was inclined to ascribe their enthusiasm to the zeal common to all authors of a new method. After my experimental experience I never doubted that transfusion of cadaver blood may give clinical results in no respect worse than those from using the blood of live donors. The assertion, however, that transfusions of cadaver blood sometimes give even better results than those of blood from live donors seemed to me to be wholly improbable. Nevertheless, my own clinical experience has convinced me that this fact is really true. It was shown by the quantity and quality of the reactions after transfusion. I realize that our series of 42 cases is still too small for making final conclusions, but the general impression is decidedly in favour of the fact that reactions after transfusing cadaver blood are much rarer and are much less conspicuous. For instance, in all our 42 cases a reaction was seen only six times in very seriously ill patients, principally with diseases of the hsemopoietic system. In no preceding series in our large experience?over 1,000 transfusions using citrated blood as well as the direct method?have we observed so few reactions; in fact, they used to amount to 60 and even 70 per cent. The following case illustrates the contrast between the two methods:? The patient was suffering from carcinoma in the caecum, with severe anajmia, in consequence of which he received four transfusions. At the first two he had fresh citrated blood from two donors of a corresponding group, and in both instance? the transfusion was accompanied by an extremely strong reaction, with a severe rigor, headache, collapse, and an eruption on the face. At the third transfusion he had 500 c.cm. of blood from a corpse, also of a corresponding group. This was accompanied only by a rise of temperature up to 101 ?F. There were no symptoms and his general condition was good. Once again he received fresh citrated blood from a new donor of a corresponding frroup, and this transfusion was again accompanied by a precisely similar reaction?rigor, rash, and collapse. We used an absolutelv identical method of preparing the apparatus, the salt and citrate solutions in all cases of transfusion, so as to exclude the possibility of any difference in the reactions being due to these. How can this be explained? _
755
the transfusing of cadaver blood was without our adding any anticoagulant. The fact, discovered by Skundina, that in some cases there is no coagulation, or rather on the contrary a ' disagulation' of cadaver blood, is in itself of great theoretical and practical interest, and will doubtless be Of the six cases five a great advantage for the method. had no reactions. The second great advantage of transfused cadaver blood that we have observed is that the increase of haemoglobin and red cells in the patient is higher than that usually observed after transfusions of an identical quantity of blood from live donors. The following figures show the amount of improvement in a patient with chloranaemia. She had a transfusion of 400 c.cm. of cadaver blood of the corresponding group, which had been preserved for 11 days. In six
cases
performed
Before transfusion
After transfusion
(28th May) (29th May) (10th June) Hemoglobin
Red cells White cells
33 per cent 40 per cent 53 per cent
..
..
2,300,000
..
5,200
3,000,000 5,600
4,250,000 6,200
These increases after transfusion of cadaver blood
can
only be explained by its sharp stimulation of the haemopoietic system. The action seems to be very variable, and in a number of cases we noted a much milder reaction in the blood count, as shown by a very slight leukocytosis, and by the absence of any great deviation in the Arneth count. These differences of reaction probably depend upon differences in the biological composition, which in its turn may be dependent upon the cause of death of the cadaver from which the
These questions still need further was taken. investigation. It is extremely interesting to leam that Professor V. P. Filatov, who is working on transplantation of the cornea, has arrived at a similar conclusion?that the transplanted cornea from the cadaver eye generally 'takes' better than that from a live donor (see Lancet, 1937 1, 1395). blood
Economic advantages Besides the general value of the method of transfusing cadaver blood lias also some advantages from the point of view of organization. In the first place, the dead body can be exonerated from the suspicion of disease with much greater certainty, since the most elaborate examination of a living donor is limited to clinical, serological, and radiological methods, while the postexamination may include an mortem exhaustive pathological investigation of all the organs. The other advantage is on the grounds of economy. The supply is cheap, and with an efficient organization it is possible to have always a, stock of this blood in any quantity an illustration the necessary for clinical needs. As following instance will suffice:? The cadaver was that of a man of athletic constitution, a wrestler, who had died suddenly of cerebral haemorrhage. Five hours after his death *2,800 c.cm. of blood was taken from him and received into citrate solution. Examination of the blood for syphilis and malaria gave negative results, and bacteriologically it, proved sterile. The medico-legal autopsy did not reveal after any signs of infectious disease. This blood, different periods of storing, was transfused into on the c.cm. 8th of five patients?500 day preservation to a woman with secondary anaemia; 500 c.cm. on the with a to 8th day pulmonary empyema ; 450 c.cm. patient on the 9th day to a patient with a carcinoma of the on the 11th day to another patient 400 c.cm. stomach: with empyema; and 400 c.cm. on the 11th day to a In all these cases the woman with pernicious anaemia. transfusion had the usual favourable effect. Thus the analysis of my own material leads me to the conclusion that the method of transfusing cadaver blood has a number of very definite advantages. It is true, however, that these advantages can be made use of in practice only with widespread and efficient organization for procuring the cadaver blood, _
THE INDIAN MEDICAL GAZETTE
756
[Dec.,
1937
and this is only possible in large centres. In practice the normal organization of transfusing such blood is still meeting a great many difficulties, chiefly from medico-judicial institutions. In spite of the fact that there is a large body of supporting evidence for its value and that full sanction has been obtained for taking blood from cases of sudden death with the observance of certain formalities, the medical men at the courts of justice were unwilling to allow the blood of bodies that are at their disposal to be drawn for clinical needs. Yet here, by an active co-operation with those in charge of local mortuaries, there is opportunity for a further practical development of the method of obtaining cadaver blood.
method of carrying out the treatment and presentation of twenty cases. It has long been noted that creosote, guaiacol and their derivatives have an almost specific action on the secondary infection occurring in open pulmonary tuberculosis but no beneficial effect on the tuberculous process -per se. The literature on the therapeutic value of these substances in non-tuberculous lung infections is scant and indefinite. The purpose of this sti^dy was to investigate the effects of one of these substances, guaiacol, on the course of acute and chronic nontuberculous lung abscess.
Prejudices
Guaiacol, phenol ester, was isolated in crystalline form in 1887 by Behal and Chosy. It is a colourless or yellow crystalline mass which darkens on exposure to air or light, melts at 28?C. and remains liquid for a long time even at lower temperature, boils at 20i?C., is insoluble in water and has an agreeable aromatic odour. Attempts to reduce its toxic and irritating properties by esterification have resulted in the preparation of numerous derivatives, many of which are soluble and practically innocuous. If guaiacol or any of its esters is to have any direct action on any pathologic condition in the lungs, it is reasonable to expect that it. will be excreted through them. Bufalini in 1904 reported that guaiacol, when administered orally, was not excreted through the lungs. In 1915 Hofbauer showed that, when injected hypodermically, guaiacol was found to be present in large amounts in the blood, liver and spleen and somewhat less in the lungs and kidneys. It is evident then that, in order to reach the lungs, guaiacol or any of its esters must be introduced by either the hypodermic or the
There is a strong prejudice in the majority of people at the bare thought of transfusing into a live person the blood from a corpse. One need not, however, go very deeply into these subconscious prejudices to understand that they are of the same order as the primitive instincts that had to be overcome in the early days of ordinary blood transfusion. There is yet another objection put forth by the patient and his relatives. Cadaver blood in the imagination of a simple and narrow-minded person is ' involuntarily connected with ptomaines', corruption, a multitude of microbes, and with the idea that the one to whom this blood has belonged has ceased to exist, and is now exposed to the horrible process of putrefaction. It will be seen therefore that all these notions are thoroughly unscientific, and are associated with the tendency to impart- to the blood a whole with the of mystic properties connected series personality of its former host. This conception is also illogical, since in medicine there is now a wide use for blood taken from slaughter-houses, as well as for different organs, prepared in different ways and injected into the veins of a patient. Everyone has become accustomed to this, and nobody protests against it. How much more simple and natural, then, it is to use instead of the blood of a dead animal the blood of a dead human being? Surely after a certain period man will overcome these prejudices as easily as the numerous others that have arisen during the history of the development of blood transfusion. Conclusions The transfusion of cadaver blood
seems
to be funda-
mentally established, experimentally as well as clinically. The method is not only equal to other methods of transfusion, applied in clinics, but may even have some advantages over them. Further advances may be made along the following lines; first, by a more detailed study of the biochemical changes in the blood after its death; secondly, by accumulating further clinical observations; and thirdly, by an efficient organization that will make use of the many
opportunities
Chemical
investigation
a
to collect blood
from all suitable
cadavers.
The Treatment of Lung Abscess by Means of Guaiacol Intravenously. An Analysis of Twenty Cases By C. H. NAMMACK,
m.d.
and A. M. TIBER, m.d. (Abstracted from the Journal of the American Medical Association, Vol. CIX, 31st July, 1937, p. 330) The use of guaiacol intravenously in the treatment of lung abscess was begun in the Fourth Medical Division of Bellevue Hospital in 1922. The results obtained in the early cases were sufficiently encouraging to decide us to make a more analytic study of this method of treatment. In all about fifty cases have been so treated. This article deals with the procedure and
intravenous route. Because solutions of guaiacol or its esters are somewhat irritating when given hypodermically, intravenous injections are preferred. Thus, the only derivatives of guaiacol that can be used in this study must be readily soluble in water. Of the water-soluble derivatives, potassium guaiacol sulphonate and calcium guaiacol sulphonate are the most readily available and have been used most extensively. However, these esters are inactive and must be saponified into their constituents and the active principle, guaiacol, liberated. When an aqueous solution of either of these compounds is administered intravenously, guaiacol can be recovered in the sputum, but the amount recovered is very small compared with the amount actually injected. It is evident then that, in order to obtain a large amount of guaiacol in the sputum, free guaiacol should be injected intravenously. However, guaiacol is insoluble in water; but if from 5 to 10 grains (0.3 to 0.65 gm.) of pure guaiacol is dissolved in from 1 to 2 c.c. of 95 per cent ethyl alcohol the guaiacol can be dissolved in an aqueous solution containing 2i grains (0.16 gm.) of sodium iodide. If either the iodide or the guaiacol is increased in amount, the guaiacol is precipitated out and can "be redissolved only by the addition of more alcohol. A solution of from 5 to 10 grains of guaiacol, 2 c.c. of ethyl alcohol and 18 c.c. of water containing 2J grains of sodium iodide is stable and will keep in a dark container for a number of months before the guaiacol will precipitate out. This solution was prepared for us by various companies and is the solution that gave the best results. This solution is somewhat irritating to the subcutaneous tissues and should be injected only after the blood has welled into the syringe. Pulmonary excretion op guaiacol The sputums of patients with definite lung abscesses were collected for three consecutive twenty-four-hour periods. Each sample was measured, acidified and distilled with steam and the distillate was collected in 20 c.c. portions. Each portion was tested with Millon's reagent for the presence of free phenol and if free phenol was found only in the first 20 c.c. of the distillate, it was termed one plus; if in the first and second,
CURRENT TOPICS
Dec., 1937J
two plus; if in the first, second and third, three plus, and in all four, four plus. The same procedure was followed after each patient was given an intravenous injection of 20 c.c. of guaiacol solution. When a solution 'containing free guaiacol is given intravenously to patients with, lung abscesses, their sputurns for from forty-eight to seventy-two hours after the injection contain a substance which gives a positive reaction with Millon's reagent. In view of the fact that no phenol bodies were present in the sputums of these patients for four consecutive days prior to the intravenous administration of guaiacol, it is reasonable to assume that the phenol body present in the sputum after the injection is guaiacol or a derivative of it.
While these experiments were being conducted, a patient with a putrid lung abscess was operated on in It was deemed our surgical division (thoracotomy). wise to examine chemically the drainage from the lung for the presence of volatile phenols. The drainage was collected for two consecutive days and the dressings and drainage distilled with steam. The distillate was collected in 20 c.c. portions as described previously and each portion tested with Millon's reagent. The patient was then given an intravenous injection of 20 c.c. of the guaiacol and iodide solution and the drainage and dressing for the next seventy-two hours collected and treated as before. The drainage from the lung abscess cavity contained no volatile phenol bodies; but, following the intravenous administration of the guaiacol solution, the drainage from the abscess cavity contained a volatile phenol which gave a positive reaction with Millon's reagent. It is evident, then, that when guaiacol .is injected intravenously it is excreted through the lungs of patients with lung abscesses as a volatile phenol body.
Summary of
treated cases with two- to five-year folloiv up Total Cured Deaths
Cases Duration of symptoms Less than 3 months (acute) More than months 3 ..
(chronic) Site of abscesses Solitary R. U. L. R. M. L. R. L. L. L. U. L. L. L. L.
..
..
..
..
..
..
..
..
..
4
S
8
0
12
8
4
10 0 2
9 0 2 3 2
1
..
..4
..
..
Multiple
..
Non-alcoholic
..
..
..
2
..1
R. U. L., L. L. L. L. IT. L.. L. L. L. Alcoholic Condition of gums and teeth
1 10 10
..
5
..
15 ..11
..
4
Healthy Suppurative gingivitis Treated (11) Untreated (4) Age distribution 20-29 years (3rd decade) 30-39 years (4th decade) 40-49 years (5th decade) 50-59 years (6th decade) Sex Male Female
16
20
..
..
v
0 0 ..
..
1
1 1 2 2
..
10. On discharge the patient was sent to a convalescent home and not permitted to resume work until the
roentgenograms revealed complete healing. The summarized results of twenty treated shown in the table above.
Comment The results have been satisfactory and it is noteworthy that Unger using an injectionable guaiacol solution obtained similar results at the Rudolf Virchow Hospital in Berlin. In the present study of twenty treated cases, it was found that the patients felt considerably better in a very short time, owing to the subsidence of the fever and cough and to the decrease of the daily sputum output and the loss of its foul odour. Serial roentgenograms showed early regression of the large area of pneumonitis surrounding the abscess cavity and later its actual disappearance. It is felt that the eradication of all foci of infection about the mouth, nose and throat and moderate restriction of all activities until the roentgenogram shows complete healing is very essential if the results of this type of treatment are to be permanent. Of the four deaths in this series, one was due to a malignant condition of the lung, one to traumatic subdural haunorrhage, and two to recurrence of the abscess. It is well to point out that the abscess reappeared in those patients who refused to have their infected gums treated. Because many lung abscesses heal spontaneously and because of the danger of early operation, most authorities agree that acute lung abscesses should be treated medically from six to twelve weeks before any surgical procedures are resorted to. Yet, after reviewing the literature, one is impressed with the lack of active medical treatment during this period. As the intravenous use of guaiacol causes early subsidence of the symptoms and a regression of the pathologic condition in the lung without producing any unfavourable reactions, it appears that this type of therapy should be used in the treatment of patients with acute and chronic lung abscess.
Use of
Prostigmin as a Diagnostic Myasthenia Gravis
17 3
Test of
m.d.
H. SCHEIE 4
(From the Journal of the American Medical Association Vol. CIX, 7th August, 1937, p. 413)
..
2
That prostigmin relieves the muscular weakness of myasthenia gravis has now been accepted quite generally
..
2
..
..
2 2
Treatment The following routine was adopted for the treatment of patients with acute or chronic lung abscesses:? 1. Bed rest if the rectal temperature was above 99.8 ?F. 2. Twenty-four-hour collection of sputum. 3. Temperature taken every four hours.
'
by all observers who have studied the drug. The relief furthermore, has provided new insight into the mechanisms at fault in the disease.
..
cases are
11 0
8
4
improved.
and
1
7
4. X-ray films of chest, in postero-anterior, lateral and oblique positions; repeated every three to four weeks. 5. Examination of teeth and careful mouth hygiene and extraction of decayed teeth if necessary. 6. Bronchoscopy soon after admission. 7. No tobacco or alcoholic drinks. 8. High caloric diet. 9. Intravenous injection of guaiacol every third or fourth day. All patients were given the solution until the amount of the sputum was reduced, its foul odour disappeared and the general condition of the patient
By G. D. GAMMON, 5
..
..
757
The
possibility
of
using the response to prostigmin as a diagnostic test of myasthenia has not, however, been fully appreciated It is true that Viets and Schwab have found that the weakness due to lesions of the central and peripheral nervous system was not materially improved. However the effect of prostigmin on the muscular diseases has not been systematically studied. We have accordinglv examined the action of the drug on the weakness due to a variety of diseases of the muscular system None of the patients obtained any striking' relief from
758
THE INDIAN MEDICAL GAZETTE
prostigmin. Therefore myasthenia gravis is the
only
condition examined thus far in which muscular weakness is consistently and markedly improved. For this reason it seems fair to conclude that a response to prostigmin may be used as a diagnostic test of the disease. Material and methods The
studied include four cases of myasthenia of which hyperthyroidism had developed; five cases of progressive muscular dystrophy ; two cases of myotonic dystrophy; one case of family periodic paralysis; two cases of amyotonia congenita; five normal adults, and three normal children. The patients were studied in the Neurological, Medical and Pediatric services of the University Hospital; diagnoses were made after careful study. In estimating changes in muscular contraction we observed facial movements and, wherever possible, we employed such objective tests as weight lifting, dynamometer tests and the height to which a mercury column could be blown. In some cases myographic records were made. As a test dose from 1.5 to 2 mg. of prostigmin hypodermically was used, combined with atropine sulphate 1/100 grain (0.00065 gm.). It should be emphasized that a large dose is required to obtain the desired response. Children tolerate about half the adult dose. cases
gravis, in
Effects
one
of
prostigmin
in
cases
of
muscular
disease
AND MYASTHENIA AND IN NORMAL PERSONS
Prostigmin in doses ordinarily employed in the treatmyasthenia sets up marked fibrillary tremors
ment of
in the muscles of normal persons and in all these cases of muscular disease except myasthenia. While best seen in the eyelids and tongue, the fibrillations occurred irregularly throughout the body and did not selectively affect the diseased muscle. The twitching probably
1937
[Dec.,
results from repetitive contraction of small groups of fibres in response to tonic impulses, since Brown, Dale and Feldberg have observed that muscle treated with _
physostigmine gives
a
multiple
response
to
a
single
stimulus applied to the motor nerve. In the muscular dystrophies the twitching was considerably more marked than in normal persons, indicating probably an increased sensitivity to the drug. In myasthenia gravis, in contrast to these cases, fibrillations almost never occurred; only rarely were they observed in the lids. The absence of a normal reaction suggests that the myasthenic process is generalized and widespread. While the lack of fibrillary twitching distinguished myasthenia from the other cases examined, a much For the weakness more striking difference was evident. of myasthenia was consistently and spectacularly relieved, but that of the other conditions was either not materially affected or, in some cases, was slightly increased. Thus only one of the seven patients with dystrophy obtained an increase in strength and this careful measurement to was so slight as to require demonstrate the change. The patient with periodic family paralysis was made somewhat weaker. Thus, of the various muscular diseases that we examined, myasthenia gravis alone responded to prostigmin with significant increase in the strength of muscular contractions. Since, then, others have shown that weakness due to lesions in the central and peripheral nervous systems is also not materially improved by prostigmin, a marked improvement in muscular weakness by prostigmin and the absence^ of fibrillary tremors is a diagnostic test of myasthenia. In other words, prostigmin appears specific for myasthenic weakness, since it relieves no other condition so far examined. It is possible that prostigmin may find its_ widest usefulness as a test to differentiate myasthenia from other causes of muscular weakness.
