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DIABETIC COMA

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397 enuretic teams had remained dry for four weeks he or she was allowed to enter a regular dormitory. This scheme worked very well over a year, and for the second year the boys and girls were allowed to carry on without the interference of the " psycho- I pediatrician " with equally satisfactory results. The second plan which Dr. Wile employed was to wake all male enuretics at 9 P.M., 12 midnight, 2 A.M., and 5 A.M., the child being made to get up and visit the closet. The percentage of cures in this group was somewhere in the neighbourhood of 30 to 40 per cent., while by the " team " method the results seemed slightly lower, although their assessment was more difficult. Dr. Hamill claims for his plan of putting the responsibility on the child that it greatly aids in the development of character, by encouraging the inhibition of impulses without conscious effort, while Dr. Wile says that the cured children in his series " reflect their new power in personality and in physical health, together with some intangible immeasurable advantages along the line of better emotional stability, greater intellectual application, and finer social balance." Such claims have never been made for the old-fashioned belladonna method, but the percentage of cures obtained was probably very much about the same. THE IMMUNISING DOSE OF VACCINIA. THE Rolleston Committee on Vaccination, in their report to the Ministry of Health last year, pointed out that definite experiments do not seem to have been made " to determine the minimal dose sufficient to give rise constantly in the human being to the characteristic vesicular manifestation and to immunity lasting for a reasonable time." In the light of their suggestion that " experimental observations be made to ascertain if it is feasible to increase the dilution of vaccine lymph beyond the present degree without impairing its efficiency," it is interesting to note some results obtained by Dr. Peter Clearkin,l of Tanganyika, in an investigation of vaccinal immunity in monkeys. He used a variolous strain obtained from a case of small-pox in 1920. Its virulence was maintained by alternate passage from calf to animal, and the titre was ascer- tained by the intradermal injection of 0-1 c.cm. of serial dilutions on the shaved abdomen of the monkey. The highest dilution causing vesiculation was taken as the titre, and the minimal infective dose was calculated from it. The immunity of the monkeys was tested, from 14 to 28 days later, by insertions of serial dilutions of a fresh, very active vaccine. The number of monkeys used was not large and the estimation of the minimal infective dose in this way is rough, but the experiments showed that very small quantities of vaccinia virus protect against enormous doses. The immunity given by 66 minimal doses was as strong as that given by 20,000, and protected against 50,000 minimal infective doses. In another experiment, two minimal infective doses protected against 100,000. Dr. Clearkin thinks that these results form a useful guide in the vaccination of human beings, since the dermal reactions of the monkey are very much the same as those of man. He points out, however, that the whole problem of anti-variolous immunisation is bound up with the production of a stable vaccinia virus. OPHTHALMOSCOPIC SIGNS IN HEART DISEASE A PAPER by Wallan M. Yater and Henry P. Wagener, of the Mayo Institute2 analyses the post-mortem findings in 137 cases of heart disease, in which the fundi had been examined ophthalmoscopically during life. The cases were classified first according to species of heart disease and secondly according to character of the changes observed in the fundus. 1 Brit. Jour. Exper. Path., August, 1929, p. 237. 2 Amer. Jour. Med. Sci., July, 1929, p. 105. The writers conclude that ophthalmoscopic examina- tion yields negative results in heart disease unless this is due to or associated with hypertension, coronary sclerosis, or subacute bacterial endocarditis. Of the 137 cases, 8 had subacute bacterial endocarditis, death being due to septicaemia in all cases. Embolic lesions were noted in 2 cases. Thirty-two patients were classified under the heading of hypertension ; of these, 25 died of cardiac decompensation with or without uraemia, 4 of hemiplegia, 2 after operations, and 1 after an accident. All but one out of the 32 showed sclerosis of the retinal arteries of " hyper- tension type " ; by this the authors mean generalised constriction of the calibre of the arteries with exaggera- tion of the arterial reflex stripe, irregularities in the lumen of the arteries, and arterio-venous compression. In addition to these changes, 17 showed retinitis- i.e., scattered cotton-wool patches and haemorrhages and cedema of the retina, occasionally even oedema of the disk. In three other cases there were haemorrhages not severe enough to come under the term retinitis. In this series, therefore, very nearly all those cases of heart disease which were dependent on high blood pressure alone showed retinal changes. Among 25 cases in which coronary sclerosis was found, 19 deaths had been due to causes purely cardiac and six followed operations. In many of these cases, and also in 11 cases of mixed type, high blood pressure was present and fundus changes had been recorded. These changes were often merely indicative of what the authors term senile arterio-sclerosis-that is, only an alteration in the light reflex, difficult to diagnose without any marked constriction of the retinal veins or alterations in the calibre of the arteries. Leaving these mild cases aside, the investigation showed that out of the 137 cases under review 52 had been diagnosed as having retinal arterio-sclerosis of the more severe or unmistakable type with or without retinitis. Even more interesting is the observation, already recorded, that, in the 32 cases in which hypertension was the only cause of cardiac disease discovered, typical retinal changes had been present in 31. ------ DIABETIC COMA. Dr. E. P. Joslin does well to point out that although seven years have now passed since the discovery of insulin, diabetic coma goes on taking its toll. It is, as he says, high time that deaths from this cause became very rare, and the simple outline of treatment which he sets out would go far towards achieving this if it were generally carried out. The treatment of the emergency of coma should, he says, take precedence over everything else and as soon as the diagnosis has been made insulin should be injected subcutaneously every half hour in doses of from 10-40 units or more until returning consciousness, normal respiration, and decreasing glycosuria show that recovery is beginning. To meet dehydration, a quart of normal saline should be injected sub- cutaneously at once, because in coma it is dangerous to trust to retention and absorption of liquids by the mouth or rectum. Intravenous injections are satis- factory if given slowly to avoid distension of the heart. The circulation, he suggests, may be stimu- lated by caffeine sodiobenzoate in doses of grs. 7 Iff given if necessary four-hourly. The stomach should be gently washed out so that liquids will be retained, and fluid containing about 50 g. of carbohydrate should be given in the first 24 hours. A gradual return to simpler articles of regular diet may then be made, the dose of insulin being regulated by frequent urinary tests, at first every two hours and later every four or six hours. The dose of insulin should bel5 units for a red reaction with Benedict’s solution, 10 for a yellow, and 5 for a green, and no insulin is required if the urine is sugar-free. Prevention, however, is better than treatment and the patient must be taught to avoid coma. He must never omit insulin, in Joslin’s opinion, so long as 1 Jour. Amer. Med. Assoc., 1929, xciii., 33.
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397

enuretic teams had remained dry for four weeks heor she was allowed to enter a regular dormitory.This scheme worked very well over a year, and forthe second year the boys and girls were allowed tocarry on without the interference of the " psycho- I

pediatrician " with equally satisfactory results. The

second plan which Dr. Wile employed was to wakeall male enuretics at 9 P.M., 12 midnight, 2 A.M., and5 A.M., the child being made to get up and visit thecloset. The percentage of cures in this group wassomewhere in the neighbourhood of 30 to 40 percent., while by the " team " method the resultsseemed slightly lower, although their assessment wasmore difficult. Dr. Hamill claims for his plan ofputting the responsibility on the child that it greatlyaids in the development of character, by encouragingthe inhibition of impulses without conscious effort,while Dr. Wile says that the cured children in hisseries " reflect their new power in personality and inphysical health, together with some intangibleimmeasurable advantages along the line of betteremotional stability, greater intellectual application,and finer social balance." Such claims have neverbeen made for the old-fashioned belladonna method,but the percentage of cures obtained was probablyvery much about the same.

THE IMMUNISING DOSE OF VACCINIA.

THE Rolleston Committee on Vaccination, in theirreport to the Ministry of Health last year, pointedout that definite experiments do not seem to havebeen made " to determine the minimal dose sufficientto give rise constantly in the human being to thecharacteristic vesicular manifestation and toimmunity lasting for a reasonable time." In thelight of their suggestion that " experimentalobservations be made to ascertain if it is feasible toincrease the dilution of vaccine lymph beyond thepresent degree without impairing its efficiency," itis interesting to note some results obtained by Dr.Peter Clearkin,l of Tanganyika, in an investigationof vaccinal immunity in monkeys. He used a

variolous strain obtained from a case of small-poxin 1920. Its virulence was maintained by alternatepassage from calf to animal, and the titre was ascer-tained by the intradermal injection of 0-1 c.cm. ofserial dilutions on the shaved abdomen of themonkey. The highest dilution causing vesiculationwas taken as the titre, and the minimal infective dosewas calculated from it. The immunity of the

monkeys was tested, from 14 to 28 days later, byinsertions of serial dilutions of a fresh, very activevaccine. The number of monkeys used was notlarge and the estimation of the minimal infectivedose in this way is rough, but the experimentsshowed that very small quantities of vaccinia virusprotect against enormous doses. The immunitygiven by 66 minimal doses was as strong as thatgiven by 20,000, and protected against 50,000minimal infective doses. In another experiment,two minimal infective doses protected against100,000. Dr. Clearkin thinks that these results form

a useful guide in the vaccination of human beings,since the dermal reactions of the monkey are verymuch the same as those of man. He points out,however, that the whole problem of anti-variolousimmunisation is bound up with the production of astable vaccinia virus.

OPHTHALMOSCOPIC SIGNS IN HEART DISEASEA PAPER by Wallan M. Yater and Henry P. Wagener,

of the Mayo Institute2 analyses the post-mortemfindings in 137 cases of heart disease, in which thefundi had been examined ophthalmoscopically duringlife. The cases were classified first according tospecies of heart disease and secondly according tocharacter of the changes observed in the fundus.

1 Brit. Jour. Exper. Path., August, 1929, p. 237.2 Amer. Jour. Med. Sci., July, 1929, p. 105.

The writers conclude that ophthalmoscopic examina-tion yields negative results in heart disease unlessthis is due to or associated with hypertension, coronarysclerosis, or subacute bacterial endocarditis. Of the137 cases, 8 had subacute bacterial endocarditis,death being due to septicaemia in all cases. Emboliclesions were noted in 2 cases. Thirty-two patientswere classified under the heading of hypertension ;of these, 25 died of cardiac decompensation with orwithout uraemia, 4 of hemiplegia, 2 after operations,and 1 after an accident. All but one out of the 32showed sclerosis of the retinal arteries of " hyper-tension type " ; by this the authors mean generalisedconstriction of the calibre of the arteries with exaggera-tion of the arterial reflex stripe, irregularities in thelumen of the arteries, and arterio-venous compression.In addition to these changes, 17 showed retinitis-i.e., scattered cotton-wool patches and haemorrhagesand cedema of the retina, occasionally even oedema ofthe disk. In three other cases there were haemorrhagesnot severe enough to come under the term retinitis.In this series, therefore, very nearly all those casesof heart disease which were dependent on high bloodpressure alone showed retinal changes. Among25 cases in which coronary sclerosis was found, 19deaths had been due to causes purely cardiac andsix followed operations. In many of these cases, andalso in 11 cases of mixed type, high blood pressurewas present and fundus changes had been recorded.These changes were often merely indicative of what theauthors term senile arterio-sclerosis-that is, onlyan alteration in the light reflex, difficult to diagnosewithout any marked constriction of the retinalveins or alterations in the calibre of the arteries.Leaving these mild cases aside, the investigationshowed that out of the 137 cases under review 52 hadbeen diagnosed as having retinal arterio-sclerosisof the more severe or unmistakable type with orwithout retinitis. Even more interesting is theobservation, already recorded, that, in the 32 cases inwhich hypertension was the only cause of cardiacdisease discovered, typical retinal changes had beenpresent in 31.

------

DIABETIC COMA.

Dr. E. P. Joslin does well to point out thatalthough seven years have now passed since thediscovery of insulin, diabetic coma goes on takingits toll. It is, as he says, high time that deaths fromthis cause became very rare, and the simple outlineof treatment which he sets out would go far towardsachieving this if it were generally carried out. Thetreatment of the emergency of coma should, he says,take precedence over everything else and as soon asthe diagnosis has been made insulin should be injectedsubcutaneously every half hour in doses of from10-40 units or more until returning consciousness,normal respiration, and decreasing glycosuria showthat recovery is beginning. To meet dehydration, aquart of normal saline should be injected sub-cutaneously at once, because in coma it is dangerousto trust to retention and absorption of liquids by themouth or rectum. Intravenous injections are satis-factory if given slowly to avoid distension of theheart. The circulation, he suggests, may be stimu-lated by caffeine sodiobenzoate in doses of grs. 7 Iffgiven if necessary four-hourly. The stomach shouldbe gently washed out so that liquids will be retained,and fluid containing about 50 g. of carbohydrateshould be given in the first 24 hours. A gradualreturn to simpler articles of regular diet may then bemade, the dose of insulin being regulated by frequenturinary tests, at first every two hours and laterevery four or six hours. The dose of insulin shouldbel5 units for a red reaction with Benedict’s solution,10 for a yellow, and 5 for a green, and no insulin isrequired if the urine is sugar-free.

Prevention, however, is better than treatment andthe patient must be taught to avoid coma. He mustnever omit insulin, in Joslin’s opinion, so long as

1 Jour. Amer. Med. Assoc., 1929, xciii., 33.

398

there is sugar in his urine, and irrespective of thediet he is taking he must increase the dose if he hasfever or an infection. This is an aspect of the subjectlately treated of by Dr. R. Boulin who places infec-tion in the first rank of causes predisposing to coma.The more impressive conditions such as pneumoniaand gangrene are, of course, not likely to be overlooked,but sore-throats, influenza, boile, and small infectedulcers have an importance to the diabetic which isout of all proportion to their apparent gravity. Comain a chronic diabetic accompanied by any of theabove conditions does not react easily to insulinand the prognosis is correspondingly grave. Next toinfection emphasis should be laid on fatigue, bothphysical and mental, whilst shock from trivialinjuries, and intoxication by alcohol or anaestheticsare other important precipitants of coma. Errorin the diabetic regime is another and betterrecognised factor, and in this connexion Boulinmentions especially excess of animal proteins.In some diabetics, he says, too much meat is a fargreater danger than too much fat. Surgical inter-vention is an obvious risk ; this should not, however,mean that its aid is withheld or even postponed,but only that due precautions are observed. Starva-tion he regards as a valuable weapon in the treatmentof precomatose conditions. The argument thatbecause in the normal subject it produces slightacidosis it is therefore likely to increase the acidosisof diabetes, he dismisses as unjustified by facts;many authorities have consistently used completestarvation to reduce acidosis and have found itquick and reliable. As regards diagnosis he laysstress on the gradual onset of mental and physicalfeebleness passing progressively into loss of conscious-ness. Coma never comes on unless there are largeamounts of sugar, and acetone as shown by theferric chloride test, in the urine ; but it is impossibleby urinary examination alone to estimate the degreeof acidosis, for this will depend upon the extent towhich the kidneys allow these bodies to pass. Otherand well-known signs of coma are loss of appetite,diarrhoea, vomiting, and abdominal pain, whilst theassociation of slow and ample inspiration and forcefulexpiration with a smell of acetone in the breath is,of course, conspicuous evidence of its commencement.

THE TRANSFUSION OF IMMUNISED BLOOD.

WE may reasonably look on serotherapy as beingstill in its infancy. At birth it was the idol of allbeholders ; then it seemed to lose weight and

popularity ; and now once more it shows signs ofbeing a credit to the family. Notable advanceshave been made of late years, for example, in thetherapeutic use of convalescent serum in quite anumber of diseases, such as poliomyelitis and measles.But obviously there are many difficulties in the wayof getting suitable and sufficient serum from con-valescent patients and the method has many limita-tions. The main effort is therefore concentrated onattempts to produce blood or serum with stronglyantipathogenic properties. Theoretically, it should bepossible to render whole human blood more potent inthis respect than any animal serum, but in practice ithas not proved very easy to do so. In applying themethod to the treatment of acute illnesses most ofthose working along these lines have*of necessityutilised non-specific transfusions, the donor of theblood being actively " immunised " by injection of anindifferent " antigen " such as nucleic acid or a

stock vaccine. It is customary to take the bloodwithin 24 hours-usually about six to eight hoursafter the inoculation-and give it at once to thepatient. In less acute conditions there is, of course,time in which to try more specific immunisation ofthe donor, a procedure which ought to be free fromrisk if it is done carefully. Thus in treating entericfever J. Clemens gave injections of typhoid vaccineto the donors until the agglutination-titre of the

2 Rev. de Méd., 1929, No. 4, p. 431. 3 Med. Klin., 1929, xxvi., 1021.

serum had reached a high value, and carried outtransfusion of blood to the patient without anydanger or disadvantage to the donor. Greater difficultyis likely to arise with streptococcal infections in whichimmunisation is attempted by means of autogenousvaccines, and Clemens preferred to use blood takenfrom people who had recovered from septic woundsor erysipelas, seldom employing any preliminaryinocu-lations to raise their immunity. The choice of donordepended on study of the bacterial flora of secretionsfrom the wound and of organisms obtained from thepatients’ blood, and in the few cases he describes itappears that proven streptococcal septicaemia whichhad shown no improvement after frequent injectionsof streptococcal serum and other treatment werecompletely cured. It is to be regretted that fullerdetails of these cases are not recorded, but so far asthey go they support the view that immunisation of adonor by autogenous streptococcal vaccines as a

preliminary to blood transfusion might be carried outin such a way as to prove useful in such conditionsas subacute malignant endocarditis. Some of thework done in this country has indicated that a

similar course of treatment may prove of value inconditions of chronic toxaemia such as are sometimespresent in rheumatoid arthritis or ulcerative colitis.With highly virulent organisms the process ofimmunisation is likely to take a considerable time,but in good hands it should certainly not be dangerous.In spite of the practical and theoretical obstacleswhich begin to crop up as soon as the subject is closelyexamined there are undoubted possibilities in thisline of treatment, and it is not too much to hope thatsome of them may soon be realised.

SPECIAL GLASS IN SCHOOL WINDOWS.

OPINION still differs about the value of havingschool-room windows made of glass which is perviousto ultra-violet rays. We know that ordinary glasscuts off most of these rays, including those of shortestwave-length which are said to be peculiarly beneficialto health; we also know that specially preparedglass will let such rays through ; further, we maytake it as proved that exposure to these short raysis often beneficial to weakly children. Here, then,is evidently a prima facie case for practical experiment,and such an experiment has now been made. In 1925a test undertaken in a Smethwick school showedstriking benefit to the health and nutrition of childrenwho had their lessons in a class-room with windows ofvita-glass, which is perhaps the best-known varietyof special window glass of the kind under considera-tion. These results got a good deal of publicity, butit was felt that the small number of children (30)and the lack of adequate controls made their reliabilitydoubtful. Therefore last year, at the instance of theBoard of Education, a thorough investigation was madein which a large group of children (240 in all) was keptunder more elaborate observation. In his annualreport Dr. Paul, the school medical officer for Smeth-wick, records the method and results of this research.Two classes were selected in each of three differentschools, great care being taken to ensure that eachpair contained children of the same average age,5 8 and 10 respectively, of the same social status,and with similar school curriculum and environment.In each group one class was kept in a room withspecial windows, and for over a year from May, 1927,careful records were kept of the children’s height andweight, and of their haemoglobin index by von Fleischel’smethod, whilst educational tests were also systematic-ally conducted. From the tables showing the figuresat the beginning and end of the experiment, whichare set out in the report, it appears that growth wasin no way greater in the vita-glass classes than amongthe controls, whilst the educational tests had incon-clusive results, the most favourable figures beingspread fairly evenly over both sets of classes. Theaverage attendances were also no better in the vita-glass classes. On the other hand, the haemoglobincontent figures were consistently better in the vita-


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