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CONVALESCENT SERUM IN THE PROPHYLAXIS AND TREATMENT OF INFECTIOUS DISEASES DUE TO FILTRABLE VIRUSES.
977
POST-GRADUATE LECTURES WE now conclude our series of abstracts of some over that age. D. N. Nabarro, who has been one of the lectures delivered at the recent post-graduate of the foremost in this country in the practical use of The courses measles convalescent serum, gives 5 c.cm. for children courses in London teaching hospitals. St. Mary’s, up to 3 and 7 c.cm. above that age. At the London in at and are steadily growing popularity for instance, the average attendance has this year Hospital we start with a dose of 2 c.cm. for children been about 200. The lectures summarised below up to 18 months, increasing the dose up to 5 c.cm. were delivered at University College Hospital (Dr. for those of 5 years ; above that age 1 c.cm. is added Himsworth) and the London Hospital (Dr. Bedson, for each year up to a maximum of 10 c.cm. Of course one cannot hope for 100 per cent. success in a procedure Dr. Hutchison, and Dr. O’Donovan). like this, but the results are remarkably good. Nabarro obtained complete protection in 98-1per cent. CONVALESCENT SERUM IN THE PROPHYLAXIS of 625 children appropriately injected before the fifth day and the successes of others reported in the AND TREATMENT OF INFECTIOUS DISEASES literature give an average figure of about 90 per cent. TO FILTRABLE DUE VIRUSES. The collection and preparation of the convalescent (DR. S. P. BEDSON.) serum is not easy for the individual practitioner, but this can be got over by giving whole blood, double FEEL is for me to on the I that there no need enlarge the dosage suggested for serum being employed. an to the of medicine of intimate importance practice Naturally it would still be necessary to ascertain study of the filtrable viruses. It will suffice if I remind that the donor gave a negative Wassermann reaction you that such diseases as measles, mumps, smallentails a delay of two days), and suitable (which pox, chicken-pox, zoster, poliomyelitis, encephalitis are not always available. convalescents However, common the influenza and cold, possibly lethargica, are due to agents of this class. And the question the serum of adults who have had measles, though of the nature of this group of disease agents, interesting not as potent as convalescent serum, has protective has obtained though it be, will have to be dismissed with the brief power and M. Burn in Birmingham an dose of results, very satisfactory using average statement that the majority of investigators, in this 7 c.cm. of adult serum for children under 5. Failing at consider these viruses to be country any rate, living a of either convalescent or adult serum the supply akin to bacteria. the things probably The mechanism of the immunity to filtrable viruses, whole blood of the parents might be used, provided, of course, that they had had measles and I would however, concerns us here and is entitled, therefore, suggest giving 10 c.cm. in the early days of the incubato less summary treatment. In the past there has tion period. Probably with this dose of adult whole been a manifest tendency in the study of these viruses blood even given early the percentage of children to exaggerate the superficial differences between them and the cultivable bacteria and to overlook funda- completely protected would not be very high and a of the disease might be expected in the mental similarities and nowhere has this tendency modified attack of cases. majority been more marked than in the field of immunity. Anterior poliomyelitis.-This is another disease in It has been held that immunity to a filtrable virus which convalescent serum has proved of considerable has a mechanism different from a bacterial immunity -that it is a pure tissue immunity in which humoral value. In this case the serum is used therapeutically antibodies play little or no part. This view is being and to be successful it must be given early (first of disease). This, of course, is a difficulty, steadily disproved and recent research has shown three days from for, apart epidemics, it is not easy to make a that in the immune state to the majority of filtrable for the use of serum to be diagnosis early enough viruses specific antibodies play an important role. this can be done the results while. But where worth of from diseases blood such The people recovering are surprisingly good, as is demonstrated by the recent as measles, small-pox, or poliomyelitis, for example, contains specific immune bodies for the invading experience of serum therapy in Winnipeg. Sixty-six virus in considerable concentration and I wish to show cases received serum, only four of these showed residual paralyses and none died, whereas of 54 that how this fact can be made use of practically. did not have serum 34 developed residual paralyses Measles.-The serum collected in the early weeks and 6 died ; the dose employed was 20 c.cm. after defervescence can be used either to prevent or It has been shown recently at the modify an attack of this disease when it is possible intramuscularly. Lister Institute that it is possible to prepare an antito administer it during the incubation period. Given serum in the horse which is as effective during the first five days after exposure to infection, poliomyelitic as convalescent serum and can be concentrated in the convalescent serum in an adequate dose will ensure same way as diphtheria or scarlet fever antitoxin.! complete protection and when injected from the Post-vaccinal encephalitis.-Although with the sixth to ninth day after exposure will modify the form of vaccination now in use cases of postmodified attack ; after that time the serum is without effect. vaccinal encephalitis will probably become rarer, In an institution such as a hospital one aims at is to bear in mind that the use of serum of it as well giving complete protection for obvious reasons, but in vaccinated has therapeutic possirecently to whether one decides general practice protect bilities. Sir Thomas persons Horder was the first to apply the or to disease a modified attack against produce 5 c.cm. intrathecally in a case of postwill depend on the individual case. In all sickly this, giving vaccinal encephalitis ; recovery was rapid and children, and those under two years, complete protection is indicated, but in robust children over two complete. J. Heckman in Holland treated 11 cases years it is preferable to allow them to have a modified with serum and 9 recovered completely. One of attack of the disease for in this way they acquire an the cases which died was moribund when serum was active immunity and the modified disease is a trivial first given, the other succumbed despite repeated affair. As regards dosage, some authorities recommend Dr. G. F. Petrie (Lister Institute, Elstree, Herts.) informs .5 c.cm. for children under 5 and 10 c.cm. for those me1 that only a limited supply of this serum is available as yet.
978
POST-GRADUATE LECTURES.
of serum. The dose he employed was Absorption of the sugar does not then occur, since, intravenously, repeated in some cases at it normally takes place in the duodenum and not. intervals of 24 or even 12 hours. The response to from the stomach. Insulin, if given, is consequently the serum was quite dramatic, the temperature falling liable to send the patient into hypoglycaemic coma. and the symptoms abating within a few hours of For intravenous injection 10 per cent. glucose in. the serum. likewise the is used; this is prepared by adding 1 drachm saline Gruneberg reported giving treatment of two cases with serum, both of which (4 g.) of salt and 60 g. of glucose to a pint of water, recovered. As in the case of poliomyelitis, recent and sterilising by boiling. The following technique. work at the Lister Institute has shown that it is of injection has been adopted in hospital. possible to prepare an antivaccinal serum in the A Wassermann needle No. 19 is used because the horse, which will render recourse to convalescent serum fine bore only allows the fluid to run slowly. In a. unnecessary.2 patient with collapsed veins the difficulty of introducOther conditions.-Encephalomyelitis, very similar ing the needle may be obviated by the method to that appearing after vaccination, may occur as a suggested by Sir Thomas Lewis. A sphygmomanocomplication of infectious diseases such as measles, meter cuff is put on the arm well above the antesmall-pox, chicken-pox, and zoster, and the success cubital fossa, the pressure is raised to 200 mm. which has attended the use of convalescent serum in for two minutes in order to stop all arterial blood post-vaccinal encephalitis makes the use of the flow, and then dropped to 80 mm., a pressure which appropriate convalescent serum in these other con- congests the veins but allows the full development of ditions well worth a trial. Mumps, too, is a filtrable reactive hypersemia after the arterial obstruction. virus disease which produces a solid and lasting If this procedure is not sufficient the vein may be immunity and its long incubation period gives ample rubbed or flicked or the arm may be immersed in opportunity for the prophylactic administration of warm water. It is important that as the flow is convalescent serum. I put these suggestions before slow the temperature of the injected fluid should be you for your consideration. They seem worth a trial 106° F. ; if too high the patient sweats and may and indicate the way in which the use of convalescentI collapse ; if too low he may have a rigor. When the serum might be extended. needle has been introduced, the pressure in th& sphygmomanometer is released and the rubber tubing from the feed funnel is connected to the, RECENT ADVANCES IN THE TREATMENT needle, the arm is immobilised by a roller towel and. OF DIABETES. sandbags, and the tubing is strapped to the forearm.. Subcutaneous injection of insulin may be used H. P. HIMSWORTH.) (DR. if the circulation is good, but otherwise its addition. FOR the last two years that method of treatment to the fluid for intravenous injection is essential.. in which the patient receives a comparatively high During coma 1 unit of insulin accounts for approxiproportion of carbohydrate and little fat has been mately 1 g. of glucose ; 500 c.cm. of 10 per cent. tried at University College Hospital. The method are therefore run in slowly and 50 units. saline has been found very successful with the ordinary glucose of insulin given by the route indicated. This isdiabetic patient. Ketosis is much better controlled, continued until the patient comes out of coma. there is less tendency to coma and to infection, and the of this method is that the patient The general health is better. Furthermore, the diet is whileadvantage still unconscious cannot swing over from diabetic cheaper, less obvious to others, more palatable, and to hypoglycsemic coma because the insulin is therefore more likely to be adhered to. The disWhen the patient continuously covered by advantage is that when put on to the diet the patient, is definitely out of coma 50sugar. of glucose by the mouth g. if not carefully watched, may drift during the first and 25 units of insulin subcutaneously are given every week when his urine is just becoming sugar-free three the proportion of sugar being raised hours, into acute hypoglycaemia. because insulin is more efficient out of coma. Th& Diabetic coma is the result of poisoning by acetone’ urine is now tested each time before giving sugar, bodies, and the treatment consists of their removal. and when the acetone bodies disappear the patient In a normal person an increase of carbohydrate in is on to a diet. Some patients are so dehydrated put the diet will remove acetone bodies, and similarly that even when out of coma they benefit from in diabetic coma will enable them to be burnt
injections 10
c.cm.
,
,
sugar off ; but the diabetic will need insulin to enable him to utilise the sugar. Both sugar and insulin are necessary to the body for the removal of acetone’ bodies in normal or diabetic individuals. Indeed, the customary thought of treating diabetic coma , by insulin, covered with sugar as a safeguard against hypoglycsemia, should be reversed. Sugar is what must be given, and enough insulin provided to enable the sugar in association with insulin to remove the: otherwise fatal ketosis. In the treatment of diabetic coma sugar may be ’
intravenous saline. Where circumstances will not permit continuous. infusion, intravenous injection of the above amounts. of glucose and of insulin should be given every two, hours. But these abrupt massive injections do not, produce such a smooth, sustained, and sure effect, can be obtained by the continuous slow method. If intravenous injection is impossible, in spite o-i£ considerable danger, glucose should be given by the stomach-tube. If this is done, the ratio of glucose to subcutaneous insulin must be raised to at least g. to 1 unit because the absorption of the glucose the or the intravenous rectum, by mouth, by given by be slow and incomplete on account of dilatation injection. Rectal administration is unsatisfactory may of the stomach. There is no harm in giving excess because the sugar is absorbed -only slightly andl of there is serious danger in giving too littlesugar ; irregularly. Oral administration, often the only wayT the of insulin. available, is unsatisfactory because in many of thesein The presence commonest cases of diabetic intoxication e cases, especially where there has been vomiting, the are those in which the patient is drowsy but amenable. stomach is dilated and the pylorus in spasm. to treatment. All that it is necessary to do in these. 2 As announced by the Ministry of Health this serum iss cases is to give, orally, 50 g. of glucose and, subavailable for use in cases of P.V.E., and can be had on application to the Lister Institute, Chelsea Bridge-road, London, S.W.:- cutaneously, 25 units of insulin every three hours ,
:
as
j
,
;
2
POST-GRADUATE LECTURES WE now conclude our series of abstracts of some over that age. D. N. Nabarro, who has been one of the lectures delivered at the recent post-graduate of the foremost in this country in the practical use of The courses measles convalescent serum, gives 5 c.cm. for children courses in London teaching hospitals. St. Mary’s, up to 3 and 7 c.cm. above that age. At the London in at and are steadily growing popularity for instance, the average attendance has this year Hospital we start with a dose of 2 c.cm. for children been about 200. The lectures summarised below up to 18 months, increasing the dose up to 5 c.cm. were delivered at University College Hospital (Dr. for those of 5 years ; above that age 1 c.cm. is added Himsworth) and the London Hospital (Dr. Bedson, for each year up to a maximum of 10 c.cm. Of course one cannot hope for 100 per cent. success in a procedure Dr. Hutchison, and Dr. O’Donovan). like this, but the results are remarkably good. Nabarro obtained complete protection in 98-1per cent. CONVALESCENT SERUM IN THE PROPHYLAXIS of 625 children appropriately injected before the fifth day and the successes of others reported in the AND TREATMENT OF INFECTIOUS DISEASES literature give an average figure of about 90 per cent. TO FILTRABLE DUE VIRUSES. The collection and preparation of the convalescent (DR. S. P. BEDSON.) serum is not easy for the individual practitioner, but this can be got over by giving whole blood, double FEEL is for me to on the I that there no need enlarge the dosage suggested for serum being employed. an to the of medicine of intimate importance practice Naturally it would still be necessary to ascertain study of the filtrable viruses. It will suffice if I remind that the donor gave a negative Wassermann reaction you that such diseases as measles, mumps, smallentails a delay of two days), and suitable (which pox, chicken-pox, zoster, poliomyelitis, encephalitis are not always available. convalescents However, common the influenza and cold, possibly lethargica, are due to agents of this class. And the question the serum of adults who have had measles, though of the nature of this group of disease agents, interesting not as potent as convalescent serum, has protective has obtained though it be, will have to be dismissed with the brief power and M. Burn in Birmingham an dose of results, very satisfactory using average statement that the majority of investigators, in this 7 c.cm. of adult serum for children under 5. Failing at consider these viruses to be country any rate, living a of either convalescent or adult serum the supply akin to bacteria. the things probably The mechanism of the immunity to filtrable viruses, whole blood of the parents might be used, provided, of course, that they had had measles and I would however, concerns us here and is entitled, therefore, suggest giving 10 c.cm. in the early days of the incubato less summary treatment. In the past there has tion period. Probably with this dose of adult whole been a manifest tendency in the study of these viruses blood even given early the percentage of children to exaggerate the superficial differences between them and the cultivable bacteria and to overlook funda- completely protected would not be very high and a of the disease might be expected in the mental similarities and nowhere has this tendency modified attack of cases. majority been more marked than in the field of immunity. Anterior poliomyelitis.-This is another disease in It has been held that immunity to a filtrable virus which convalescent serum has proved of considerable has a mechanism different from a bacterial immunity -that it is a pure tissue immunity in which humoral value. In this case the serum is used therapeutically antibodies play little or no part. This view is being and to be successful it must be given early (first of disease). This, of course, is a difficulty, steadily disproved and recent research has shown three days from for, apart epidemics, it is not easy to make a that in the immune state to the majority of filtrable for the use of serum to be diagnosis early enough viruses specific antibodies play an important role. this can be done the results while. But where worth of from diseases blood such The people recovering are surprisingly good, as is demonstrated by the recent as measles, small-pox, or poliomyelitis, for example, contains specific immune bodies for the invading experience of serum therapy in Winnipeg. Sixty-six virus in considerable concentration and I wish to show cases received serum, only four of these showed residual paralyses and none died, whereas of 54 that how this fact can be made use of practically. did not have serum 34 developed residual paralyses Measles.-The serum collected in the early weeks and 6 died ; the dose employed was 20 c.cm. after defervescence can be used either to prevent or It has been shown recently at the modify an attack of this disease when it is possible intramuscularly. Lister Institute that it is possible to prepare an antito administer it during the incubation period. Given serum in the horse which is as effective during the first five days after exposure to infection, poliomyelitic as convalescent serum and can be concentrated in the convalescent serum in an adequate dose will ensure same way as diphtheria or scarlet fever antitoxin.! complete protection and when injected from the Post-vaccinal encephalitis.-Although with the sixth to ninth day after exposure will modify the form of vaccination now in use cases of postmodified attack ; after that time the serum is without effect. vaccinal encephalitis will probably become rarer, In an institution such as a hospital one aims at is to bear in mind that the use of serum of it as well giving complete protection for obvious reasons, but in vaccinated has therapeutic possirecently to whether one decides general practice protect bilities. Sir Thomas persons Horder was the first to apply the or to disease a modified attack against produce 5 c.cm. intrathecally in a case of postwill depend on the individual case. In all sickly this, giving vaccinal encephalitis ; recovery was rapid and children, and those under two years, complete protection is indicated, but in robust children over two complete. J. Heckman in Holland treated 11 cases years it is preferable to allow them to have a modified with serum and 9 recovered completely. One of attack of the disease for in this way they acquire an the cases which died was moribund when serum was active immunity and the modified disease is a trivial first given, the other succumbed despite repeated affair. As regards dosage, some authorities recommend Dr. G. F. Petrie (Lister Institute, Elstree, Herts.) informs .5 c.cm. for children under 5 and 10 c.cm. for those me1 that only a limited supply of this serum is available as yet.
978
POST-GRADUATE LECTURES.
of serum. The dose he employed was Absorption of the sugar does not then occur, since, intravenously, repeated in some cases at it normally takes place in the duodenum and not. intervals of 24 or even 12 hours. The response to from the stomach. Insulin, if given, is consequently the serum was quite dramatic, the temperature falling liable to send the patient into hypoglycaemic coma. and the symptoms abating within a few hours of For intravenous injection 10 per cent. glucose in. the serum. likewise the is used; this is prepared by adding 1 drachm saline Gruneberg reported giving treatment of two cases with serum, both of which (4 g.) of salt and 60 g. of glucose to a pint of water, recovered. As in the case of poliomyelitis, recent and sterilising by boiling. The following technique. work at the Lister Institute has shown that it is of injection has been adopted in hospital. possible to prepare an antivaccinal serum in the A Wassermann needle No. 19 is used because the horse, which will render recourse to convalescent serum fine bore only allows the fluid to run slowly. In a. unnecessary.2 patient with collapsed veins the difficulty of introducOther conditions.-Encephalomyelitis, very similar ing the needle may be obviated by the method to that appearing after vaccination, may occur as a suggested by Sir Thomas Lewis. A sphygmomanocomplication of infectious diseases such as measles, meter cuff is put on the arm well above the antesmall-pox, chicken-pox, and zoster, and the success cubital fossa, the pressure is raised to 200 mm. which has attended the use of convalescent serum in for two minutes in order to stop all arterial blood post-vaccinal encephalitis makes the use of the flow, and then dropped to 80 mm., a pressure which appropriate convalescent serum in these other con- congests the veins but allows the full development of ditions well worth a trial. Mumps, too, is a filtrable reactive hypersemia after the arterial obstruction. virus disease which produces a solid and lasting If this procedure is not sufficient the vein may be immunity and its long incubation period gives ample rubbed or flicked or the arm may be immersed in opportunity for the prophylactic administration of warm water. It is important that as the flow is convalescent serum. I put these suggestions before slow the temperature of the injected fluid should be you for your consideration. They seem worth a trial 106° F. ; if too high the patient sweats and may and indicate the way in which the use of convalescentI collapse ; if too low he may have a rigor. When the serum might be extended. needle has been introduced, the pressure in th& sphygmomanometer is released and the rubber tubing from the feed funnel is connected to the, RECENT ADVANCES IN THE TREATMENT needle, the arm is immobilised by a roller towel and. OF DIABETES. sandbags, and the tubing is strapped to the forearm.. Subcutaneous injection of insulin may be used H. P. HIMSWORTH.) (DR. if the circulation is good, but otherwise its addition. FOR the last two years that method of treatment to the fluid for intravenous injection is essential.. in which the patient receives a comparatively high During coma 1 unit of insulin accounts for approxiproportion of carbohydrate and little fat has been mately 1 g. of glucose ; 500 c.cm. of 10 per cent. tried at University College Hospital. The method are therefore run in slowly and 50 units. saline has been found very successful with the ordinary glucose of insulin given by the route indicated. This isdiabetic patient. Ketosis is much better controlled, continued until the patient comes out of coma. there is less tendency to coma and to infection, and the of this method is that the patient The general health is better. Furthermore, the diet is whileadvantage still unconscious cannot swing over from diabetic cheaper, less obvious to others, more palatable, and to hypoglycsemic coma because the insulin is therefore more likely to be adhered to. The disWhen the patient continuously covered by advantage is that when put on to the diet the patient, is definitely out of coma 50sugar. of glucose by the mouth g. if not carefully watched, may drift during the first and 25 units of insulin subcutaneously are given every week when his urine is just becoming sugar-free three the proportion of sugar being raised hours, into acute hypoglycaemia. because insulin is more efficient out of coma. Th& Diabetic coma is the result of poisoning by acetone’ urine is now tested each time before giving sugar, bodies, and the treatment consists of their removal. and when the acetone bodies disappear the patient In a normal person an increase of carbohydrate in is on to a diet. Some patients are so dehydrated put the diet will remove acetone bodies, and similarly that even when out of coma they benefit from in diabetic coma will enable them to be burnt
injections 10
c.cm.
,
,
sugar off ; but the diabetic will need insulin to enable him to utilise the sugar. Both sugar and insulin are necessary to the body for the removal of acetone’ bodies in normal or diabetic individuals. Indeed, the customary thought of treating diabetic coma , by insulin, covered with sugar as a safeguard against hypoglycsemia, should be reversed. Sugar is what must be given, and enough insulin provided to enable the sugar in association with insulin to remove the: otherwise fatal ketosis. In the treatment of diabetic coma sugar may be ’
intravenous saline. Where circumstances will not permit continuous. infusion, intravenous injection of the above amounts. of glucose and of insulin should be given every two, hours. But these abrupt massive injections do not, produce such a smooth, sustained, and sure effect, can be obtained by the continuous slow method. If intravenous injection is impossible, in spite o-i£ considerable danger, glucose should be given by the stomach-tube. If this is done, the ratio of glucose to subcutaneous insulin must be raised to at least g. to 1 unit because the absorption of the glucose the or the intravenous rectum, by mouth, by given by be slow and incomplete on account of dilatation injection. Rectal administration is unsatisfactory may of the stomach. There is no harm in giving excess because the sugar is absorbed -only slightly andl of there is serious danger in giving too littlesugar ; irregularly. Oral administration, often the only wayT the of insulin. available, is unsatisfactory because in many of thesein The presence commonest cases of diabetic intoxication e cases, especially where there has been vomiting, the are those in which the patient is drowsy but amenable. stomach is dilated and the pylorus in spasm. to treatment. All that it is necessary to do in these. 2 As announced by the Ministry of Health this serum iss cases is to give, orally, 50 g. of glucose and, subavailable for use in cases of P.V.E., and can be had on application to the Lister Institute, Chelsea Bridge-road, London, S.W.:- cutaneously, 25 units of insulin every three hours ,
:
as
j
,
;
2