839 and there is probably a depletion rather than an excess of water as far as the bodily tissues are concerned. If, however, steps are taken to prevent the diuresis in these cases, serious symptoms may arise. LARSON, WEIR, and ROwNTREE have recorded the occurrence of such symptoms-headache, nausea, asthenia, and incoordination of movement-in three cases of diabetes insipidus in which the diuresis had been checked by the administration of pituitary extract without the patients having diminished their water- intake. Similar effects were produced in normal dogs by the administration of pituitary extract, and, believing the results to be due to water intoxication rather than to the drug, L. G. RowWNTREF 4 has now performed an extensive series of control experiments. Water in excessive amounts was administered through stomach-tubes to dogs, cats, and rabbits. In all these animals the symptoms produced were very striking. Retching and vomiting were followed by violent convulsions, similar to those produced by strychnine poisoning. These convulsions tended to recur at intervals of a few minutes, the animals in the interval being in a state of asthenia often bordering on coma. Death in coma, or during a convulsion, frequently occurred, but if recovery took place the animal was usually normal in a few hours after the cessation of water administration. In rabbits and guinea-pigs little actual vomiting occurred and the onset of convulsions was more rapid than in dogs, in whom there was frequent vomiting and sometimes diarrhoea. In rabbits it was possible to produce a condition of subacute intoxication by administering water in amounts equal to one-fourth of the body- weight daily over a long period. Careful post-mortem examination of these animals disclosed very little anatomical change in the tissues, the liver and kidneys showed a moist surface on section, but little cellular change could be made out on microscopic examination. (Edema could be seen in three situations, in the connective tissue of the renal cortex, in the distribution of the portal vein, and around the vessels of the brain. Careful control experiments seem to show that the symptoms could not be accounted for by the passage of the stomach-tube nor by gastric distension. The rapid absorption of digestive products or enzymes was also considered and negatived, and similar experiments on dogs with Eck’s fistula led to the same effects which appears to eliminate any explanation on the grounds of hepatic oedema. It is noteworthy that the symptoms could not be reproduced either by rectal or intravenous administration, though the occurrence of haemolysis made the latter series of experiments difficult to interpret. Actual measurement of the intracranial pressure showed that a definite rise occurs, and the intravenous administration of hypertonic salt solutions was effective in preventing the symptoms in subsequent experiments. From this ROwNTREE concludes that the main effects of water intoxication are due to the increased intracerebral pressure which occurs when the water-intake largely exceeds the output. This striking series ui U 1J.’Cl V dlilUIlnS’ mus 1’C V 1 V C ; interest in the possibility that water intoxication alone ; may account for many of the phenomena of uraemia. Retention of urea, of uric acid, of creatinin, and of unknown toxic nitrogenous substances have succes- sively been accused as responsible. More recently 0. L. V. DE WESSELOW, in this journal, has called J attention to the inorganic phosphorous content of the plasma in nephritis, showing that an increased concen- tration of phosphates in the blood is of perhaps greater prognostic importance even than nitrogen retention. It is to be hoped that in future work RowrTTR,EE will be able to throw further light on the relation of water intoxication to these problems, which are of the gceatest interest both to clinicians and to chemical pathologists. 3 E. E. Larson, L. G. Rowntree, and J. F. Weir: Arch. Int. Med., 1922. xxis., 306. 4 L. G. Rowntree: Arch. Int. Med., 1923, xxxii., 157. 5 O. L. V. de Wesselow: THE LANCET, ccv., 163, 1923. Annotations. A HOPEFUL OUTLOOK IN MEDICINE AND DENTISTRY. " Ne quid nimis." THE opening address to students of the Royal Dental Hospital, London, was delivered on Oct. 1st by Dr. Addison, whose message was the need of preserving a sense of proportion in the medical outlook. Pro- fessional problems must be approached from a public point of view; it was essential, he said, for the doctor or dentist to see things as the ordinary man sees them. He referred to two outstanding needs of our time as, first, the need of more know- ledge, and second, economy-the need of getting our money’s worth. Scientific research was a paying proposition, though this was not always recognised. Money spent on research brought back huge profits, not only in the saving of life but financially as well. In speaking of the means of spreading knowledge, Dr. Addison paid a tribute to THE LANCET ; it was impossible to calculate, he said, the work done by such a journal, distilling every week fresh knowledge from many sources, and keeping doctors abreast of what was being done in all parts of the world for the advancement of medical science. Dr. Addison referred to the Dentists Act of 1921 in hopeful terms, since it could not fail to raise the status of that branch of the profession of healing. Dr. William Hunter’s address to the students of Charing Cross Hospital when distributing the prizes was no less optimistic. He maintained that there was much romance to be found in our profession if the student looked out for it. The amount of knowledge which the student was required to imbibe, and periodically disgorge to the examiners, was indeed stupendous ; teachers to right, left, and in front of him volleyed and thundered out knowledge, sometimes regardless of the insoluble problem of how to get a quart of fluid into a pint pot. Yet still the day contained no more than 24 hours. Fortunately, however, the student maintained a sense of humour, which even the enthusiasm of his teachers could not altogether damp ; and the constant contact with human beings, and the interest of the combat with disease, made life in the medical profession one great adventure. Dr. Hunter proceeded to sketch the different eras in the advances of medical knowledge, making special reference to the importance, in medicine as well as surgery, of sepsis, and the recent beneficial results in mental disease arising from careful attention to septic foci. There should be no attempt, he said, to separate the different departments of medical research and knowledge, and the clinical aspect should have first place. The profession was a hard one, the emoluments, except to a few, and those chiefly in the surgical branch, were not great; but it carried with it a human interest which nothing else approached, a high purpose, and possibilities of adding to the happiness of millions of people. VACCINES IN CHRONIC OSTEOMYELITIS. IN a paper 1 read in Stockholm at the fourteenth meeting of the Nordisk Kirurgisk Forening, Prof. T. Rovsing, of Copenhagen, gave a laudatory account of the action of autogenous vaccines in cases of chronic or relapsing osteomyelitis. In the acute stage of this disease he is doubtful as to the efficacy of vaccines, but in the chronic stage they frequently act like a charm. Since 1915 he has treated 23 cases of chronic osteomyelitis with vaccines. In as many as 16 cases the infecting organism proved to be the Staphy- lococcus aureus. In four other cases the Staphy- lococcus albus, in two the typhoid bacillus, and in one the paratyphoid bacillus were found. In every 1 Hospitalstidende, August 8th, 1923.
Transcript
839
and there is probably a depletion rather than an excessof water as far as the bodily tissues are concerned.If, however, steps are taken to prevent the diuresisin these cases, serious symptoms may arise. LARSON,WEIR, and ROwNTREE have recorded the occurrenceof such symptoms-headache, nausea, asthenia, andincoordination of movement-in three cases ofdiabetes insipidus in which the diuresis had beenchecked by the administration of pituitary extractwithout the patients having diminished their water-intake. Similar effects were produced in normaldogs by the administration of pituitary extract,and, believing the results to be due to waterintoxication rather than to the drug, L. G. RowWNTREF 4has now performed an extensive series of controlexperiments.Water in excessive amounts was administered
through stomach-tubes to dogs, cats, and rabbits.In all these animals the symptoms produced werevery striking. Retching and vomiting were followedby violent convulsions, similar to those produced bystrychnine poisoning. These convulsions tended torecur at intervals of a few minutes, the animals in theinterval being in a state of asthenia often borderingon coma. Death in coma, or during a convulsion,frequently occurred, but if recovery took place theanimal was usually normal in a few hours after thecessation of water administration. In rabbits andguinea-pigs little actual vomiting occurred and theonset of convulsions was more rapid than in dogs, inwhom there was frequent vomiting and sometimesdiarrhoea. In rabbits it was possible to produce acondition of subacute intoxication by administeringwater in amounts equal to one-fourth of the body-weight daily over a long period. Careful post-mortemexamination of these animals disclosed very littleanatomical change in the tissues, the liver and kidneysshowed a moist surface on section, but little cellularchange could be made out on microscopic examination.(Edema could be seen in three situations, in theconnective tissue of the renal cortex, in the distributionof the portal vein, and around the vessels of the brain.Careful control experiments seem to show that thesymptoms could not be accounted for by the passageof the stomach-tube nor by gastric distension. Therapid absorption of digestive products or enzymes wasalso considered and negatived, and similar experimentson dogs with Eck’s fistula led to the same effects whichappears to eliminate any explanation on the groundsof hepatic oedema. It is noteworthy that thesymptoms could not be reproduced either by rectal orintravenous administration, though the occurrence ofhaemolysis made the latter series of experimentsdifficult to interpret. Actual measurement of theintracranial pressure showed that a definite rise occurs,and the intravenous administration of hypertonic saltsolutions was effective in preventing the symptomsin subsequent experiments. From this ROwNTREEconcludes that the main effects of water intoxicationare due to the increased intracerebral pressure whichoccurs when the water-intake largely exceeds theoutput.
This striking series ui U 1J.’Cl V dlilUIlnS’ mus 1’C V 1 V C ;
interest in the possibility that water intoxication alone ;may account for many of the phenomena of uraemia.Retention of urea, of uric acid, of creatinin, and ofunknown toxic nitrogenous substances have succes-sively been accused as responsible. More recently0. L. V. DE WESSELOW, in this journal, has called J
attention to the inorganic phosphorous content of theplasma in nephritis, showing that an increased concen-tration of phosphates in the blood is of perhaps greaterprognostic importance even than nitrogen retention.It is to be hoped that in future work RowrTTR,EE willbe able to throw further light on the relation of waterintoxication to these problems, which are of thegceatest interest both to clinicians and to chemicalpathologists.
3 E. E. Larson, L. G. Rowntree, and J. F. Weir: Arch. Int.Med., 1922. xxis., 306.
4 L. G. Rowntree: Arch. Int. Med., 1923, xxxii., 157.5 O. L. V. de Wesselow: THE LANCET, ccv., 163, 1923.
Annotations.
A HOPEFUL OUTLOOK IN MEDICINE AND
DENTISTRY.
" Ne quid nimis."
THE opening address to students of the RoyalDental Hospital, London, was delivered on Oct. 1st byDr. Addison, whose message was the need of preservinga sense of proportion in the medical outlook. Pro-fessional problems must be approached from a publicpoint of view; it was essential, he said, for thedoctor or dentist to see things as the ordinaryman sees them. He referred to two outstandingneeds of our time as, first, the need of more know-ledge, and second, economy-the need of getting ourmoney’s worth. Scientific research was a payingproposition, though this was not always recognised.Money spent on research brought back huge profits,not only in the saving of life but financially as well.In speaking of the means of spreading knowledge,Dr. Addison paid a tribute to THE LANCET ; it wasimpossible to calculate, he said, the work done bysuch a journal, distilling every week fresh knowledgefrom many sources, and keeping doctors abreast ofwhat was being done in all parts of the world for theadvancement of medical science. Dr. Addisonreferred to the Dentists Act of 1921 in hopefulterms, since it could not fail to raise the status ofthat branch of the profession of healing.
Dr. William Hunter’s address to the students ofCharing Cross Hospital when distributing the prizeswas no less optimistic. He maintained that therewas much romance to be found in our professionif the student looked out for it. The amount ofknowledge which the student was required to imbibe,and periodically disgorge to the examiners, was
indeed stupendous ; teachers to right, left, and infront of him volleyed and thundered out knowledge,sometimes regardless of the insoluble problem of howto get a quart of fluid into a pint pot. Yet still theday contained no more than 24 hours. Fortunately,however, the student maintained a sense of humour,which even the enthusiasm of his teachers could notaltogether damp ; and the constant contact with humanbeings, and the interest of the combat with disease,made life in the medical profession one great adventure.Dr. Hunter proceeded to sketch the different eras inthe advances of medical knowledge, making specialreference to the importance, in medicine as well assurgery, of sepsis, and the recent beneficial results inmental disease arising from careful attention toseptic foci. There should be no attempt, he said,to separate the different departments of medicalresearch and knowledge, and the clinical aspectshould have first place. The profession was a hardone, the emoluments, except to a few, and thosechiefly in the surgical branch, were not great; but itcarried with it a human interest which nothing elseapproached, a high purpose, and possibilities ofadding to the happiness of millions of people.
VACCINES IN CHRONIC OSTEOMYELITIS.IN a paper 1 read in Stockholm at the fourteenth
meeting of the Nordisk Kirurgisk Forening, Prof. T.Rovsing, of Copenhagen, gave a laudatory accountof the action of autogenous vaccines in cases of chronicor relapsing osteomyelitis. In the acute stage ofthis disease he is doubtful as to the efficacy of vaccines,but in the chronic stage they frequently act like acharm. Since 1915 he has treated 23 cases of chronicosteomyelitis with vaccines. In as many as 16 casesthe infecting organism proved to be the Staphy-lococcus aureus. In four other cases the Staphy-lococcus albus, in two the typhoid bacillus, and inone the paratyphoid bacillus were found. In every
1 Hospitalstidende, August 8th, 1923.
840
case there was a definite reaction to the injections, 1which in almost every case gave a dramatically rapidturn for the better to the course of the disease. Thiswas often the case even when the infection hadlasted for a decade or two, and had been characterisedby the persistence of fistulae or by recurrent exacerba-tions. The prompt and complete recoveries achievedin such cases showed vaccine therapy in markedcontrast to the more primitive methods of the operat-ing surgeon. Prof. Rovsing does not, however,underrate the ancillary services that the operatingsurgeon may render in such cases, and he advocatesthe operative removal of sequestra as a preliminaryto vaccine treatment. With regard to the compara-tive merits of autogenous and stock vaccines, he isemphatically in favour of the former, particularlywhen the infecting organism belongs to that largefamily generically referred to as the Staphylococcusaureus. To hope that a stock vaccine made fromone member of this group will be beneficial in agiven case of Staphylococcus aureus infection is, inhis opinion, to show a sublimely foolish belief in thepatient’s luck against heavy odds. But he admitsthere are cases in which the surgeon must suppresshis contempt for the second best and give a stockvaccine. All the three cases of osteomyelitis belong-ing to the typhoid group responded satisfactorily tovaccine treatment, and the success in one was
remarkable as the patient, aged 44, had sufferedfrom osteomyelitis of the radius since the ageof 22. Prof. Rovsing gives the name of a Londonsurgeon who diagnosed the case as one of syphilis,with the result that, wherever the patient travelled,he was pursued by mercury, iodine, and salvarsan.These remedies did no good, and when the Wasser-mann reaction was found to be negative and a historywas obtained of two attacks of typhoid fever, one atthe age of 13 and the other at the age of 20, thetyphoid character of the infection was suspected,and an autogenous vaccine, made from the typhoidbacilli found, rapidly restored the patient to com-plete health, which has been maintained during thesix years which have since elapsed.
EVIDENCE OF PATERNITY.
SOME observations made by the bench in disposingof an affiliation order appeal at the recently heldquarter sessions for the County of Devon deservenotice. Sir Francis Newbolt, K.C., the chairman, isreported in the Times of Oct. 6th to have said that-" Since the Slings by case and a recent case in the DivorceCourt, which caused a great amount of discussion, it hadbecome known, even to the general public, that the questionof paternity might often be settled by purely scientificevidence, and although that at present was beyond themeans of persons generally concerned with affiliationorders, it was a matter for careful consideration whethersteps should not be taken to circulate sufficient informationfor ordinary medical practitioners to give evidence ofcertain elementary indications. In the case under con-
sideration such evidence would have been of great value."
Any comment on these remarks must be qualified bythe fact that the report from which we quote is brief.In this connexion we recently referred to the Slingsbylegitimation action and the divorce case of Russell v.Russell, and in view of the learned chairman’s sugges-tion it may be desirable to make some further allusionto the subject. If he is referring merely to the aidswhich an expert might give in the detection of familylikeness of feature, then no doubt it is possible tosummarise and classify various points in which anexternal similarity may manifest itself, just as a
handwriting expert may draw attention to minutiaewhich judge or jury can appreciate but might notreadily discover for themselves. Since, however,affiliation proceedings usually take place at a timewhen the infant’s features are as yet immature andundeveloped a note of caution may be sounded. Inthe Slingsby case the boy was several years of age ;
1 THE LANCET, August 11th, 1923.
his features had attained a certain fixity which facili-tated the detection of resemblances, and there is nodoubt that Sir Bargrave Deane, who tried the case,must have derived much advantage from the expertknowledge of the great sculptor Sir George Frampton,whose assistance was invoked. In the Russell casethe baby was of more tender age, and Mr. Justice Hillwas careful to warn the jury against giving too muchweight to the element of physical resemblance. If, onthe other hand, Sir Francis Newbolt’s " elementaryindications " are a reference to the scientific investiga-tion of blood-groups, to which attention was drawn inthese columns in 1922,2 it is again necessary to saythat the positive results of this attractive branch ofresearch are, for juristic purposes, scarcely complete.We repeat this note of warning, since it would beunfortunate if it were generally supposed that formulaecan be broadcasted by the aid of which the paternityof a child can be with certitude ascribed to one man ordenied to another without reservations. It would bestill more unfortunate if, by a misunderstanding ofSir Francis Newbolt’s briefly summarised observations,an impression arose that medical witnesses were
prepared to supply the necessary evidence in thesecases provided that the necessary funds are forth-coming. ____
THE TREATMENT OF MALARIA.
AN opportune and valuable monograph 3 recentlypublished deals with many pressing points in thetreatment of malaria in the following order : (1) Thevalue of cinchona febrifuge ; (2) the relative meritsof the different alkaloids of cinchona in malaria;(3) the value of some tasteless preparations of quinine ;(4), (5), and (6) intramuscular, intravenous, andrectal injections of quinine ; (7) the dosage of
quinine ; (8) the examination of the urine duringquinine treatment; (9) quinine resistance. Cinchonafebrifuge is as efficient, therapeutically, as is quininein malaria, but it is much cheaper; there are many
preparations of different strengths being sold underthis name. The constitution of this drug should belegally defined ; that made by the Government ofIndia contains 54:’65 per cent. of the crystallisablealkaloids quinine, quinidin, cinchonine, and cincho-nidine. Contrary to the views of Acton, Dr. Fletcherfinds that these four crystallisable alkaloids appear tobe of equal value in bringing about the disappearanceof malarial parasites in doses of 10 gr. given twicedaily, at which strength none of them produces toxicsymptoms. The alkaloid quinoidine is much moretoxic and fails to destroy malaria parasites. Dr.Fletcher has done a real service in pointing out thatcertain tasteless preparations of quinine-i.e., quininealkaloid and euquinine-are effacious in the cure ofmalaria ; while, on the other hand, quinine tannateand quinine dicarbonate are quite useless. We arein entire agreement with what he has to say regardingthe intramuscular injection of quinine. Serious illnessand mutilation may occur as a result, and, in somecases where this has happened, the drug could havebeen equally well given by the mouth. When injectedinto the muscles quinine is not absorbed as quicklyas when taken by the mouth, neither is it more potentin preventing relapses. Quinine produces immediatenecrosis of the tissue into which it is injected ; thedead muscle is usually absorbed in a few weeks, butmay remain as a source of danger, forming an excellentmedium for the growth of bacteria which may gainaccess either from without or from the blood-stream.These injections, then, should be reserved for patientswho are dangerously ill with malaria, or for thosewho are comatose, or for some reason unable toswallow. In the same way the intravenous injectionsof quinine should be only reserved for the most
2 THE LANCET, 1922, ii., 285.3 Notes on the Treatment of Malaria with the Alkaloids of
Cinchona, No. 18. Studies from the Institute for MedicalResearch, Kuala Lumpur, Federated Malay States. By WilliamFletcher, M.D. Cambridge, Bacteriologist Institute for MedicalResearch, Kuala Lumpur. London: J. Bale, Sons, andDanielsson, Ltd. 1923. Pp. 91. 6s.
