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1102 Annotations. THE OPTICAL PROPERTIES OF THE CEREBRO- SPINAL FLUID. "Ne quid nimis." DURING the last 20 years the cerebro-spinal fluid has .provided a rich field for those who have the desire and ability to search for the hidden things in the chemistry and physics of the body. The chief value of this fluid from the point of view of research lies in the constancy of its normal chemical and physical com- position, and in its comparative freedom from the proteins and protein compounds which complicate the physico-chemical examination of the blood. Since Mestrezat settled the normal chemical composition of the fluid many investigators have examined the - relation of variations in this to variations in blood chemistry with fruitful results. It may even be said that the chemistry of the cerebro-spinal fluid in disease has in many ways helped us to understand the chemistry of the blood. More recently the finer methods of the physical laboratory have been applied to the cerebro-spinal fluid, partly from a pure desire for knowledge, and partly in an attempt to find new methods which will help in the diagnosis of disease. Electric properties, such as electro-conductivity and the electric charge of the proteins, have already been examined, and now the optical properties of the fluid - are being investigated by modern instruments. Two recent papers deal with the refractility of the fluid and its power of absorption of the ultra-violet end of the spectrum. Penfold and Price, 1 who have investigated the refractile properties of the fluid with the Zeiss dipping refractometer, had the results of several previous workers as a basis for their investiga- tions. It may be said at once that their results agree - closely with what had previously been found. They establish the normal refractility at 1-33510 in the .-adult and 1-33508 in the child, with variations of no more than six units in the fifth decimal place. Any greater variation they have found to be pathological, and to indicate some disturbance either in the - chemistry of the cerebro-spinal fluid alone or more commonly in the chemistry of the blood. The chief value of their work appears to lie in the correlation which they have sought and sometimes obtained between the changes in the proportions of the chemical °constituents of the cerebro-spinal fluid and the alterations in refraction. Thus in nephritis and diabetes the refractility as calculated from the chemical examination might be identical with that obtained directly by the refractometer. When this parallelism was not obtained it was considered that - some chemical substance which had not been investi- ,gated in the routine examination was present in abnormal concentration, and a further examination might reveal this. In diseases of the central nervous ,system there was often little departure from the normal refractility, since an increase in protein might be compensated by a reduction in the chlorides or glucose. Increase of refractility was much more ..common than reduction, and was the rule in many .diseases of the nervous system, such as cerebral and .,gpinal tumour. On the whole, however, the refrac- tometry of the cerebro-spinal fluid appeared to be of more clinical value in general diseases such as uraemia ,and diabetes than in diseases confined to the central -nervous system. The absorption of the ultra-violet end of the copper arc spectrum has been studied by Fretson Skinner,2 who hoped to gain by this means some indication of the nature of the colloids present in the cerebro-spinal fluid. In this he was disappointed, for 1 Penfold, W. J., and Price, C. A. E.: Med. Jour. Australia, Sept. 28th, p. 424. 2 Skinner, F. Fretson: Jour. Neur. and Psycho-path., 1929, x., 97. the absorption of ultra-violet rays appeared to have no necessary relation to the colloids in the fluid. Nor were any characteristic bands observed. He did, however, find important variations from the normal in certain diseases. Thus tabes dorsalis con- stantly caused an increased absorption at the ultra- violet end of the spectrum, general paralysis rather more, and tuberculous meningitis much more. Some diseases, such as disseminated sclerosis, might, how- ever, give almost normal spectra. The number of fluids examined and the exact spectrum given by each is not stated. This method of examining the cerebro-spinal fluid is of some theoretical interest, but until the results which it gives can be correlated with changes in the constituents of the fluid it is likely to be of little practical value. SNAKE-BITE AND ANTIVENIN. SNAKE-BITE does occasionally, if rarely, give rise to alarming symptoms in this country, as our correspondence columns recently testified.1 Our only poisonous snake is the adder, but in the United States of America rattlesnakes are responsible for the majority of cases, although the number of bites by copper-heads exceeds those of any other one species. In the current Bulletin of the Antivenin Institute of America, R. H. Hutchison has collected 607 case reports of snake-bite for the year 1928, and found that the species of snake could be identified with a fair degree of accuracy in three-quarters of them. From April until July the risk of snake-bite increases steadily, but it b(gins to decline again in the middle of September, and has practically ceased to exist by the middle of October. The greatest danger seems to lie in picking up or reaching for something on the ground. because any movement towards an unseen snake will elicit a lightning-like defensive bite. The symptoms vary considerably, but in most cases swelling and pain appeared early, and were the outstanding features. If the bitten part did not hurt and swell, the snake was either non-poisonous or its injection apparatus was not working properly. Other symptoms noticed were weakness, giddiness, haemorrhage, difficulty in breath- ing, nausea and vomiting, as well as a host of occasional distuibances. The reports include almost every conceivable method of treatment, from the application of a freshly killed chicken to cauterisation, and specific treatment with antivenin. From this abundance of r c -)mmendations three first-aid methods have emerged as having real value. The first is the application of a tourniquet above the bite, drawn tightly enough to obstruct venous return. It should be released every quarter of an hour for at least two minutes to re-establish the circulation, its purpose being only to diminish the rate at which the venom enters the general circulation. The second measure is a crucial incision over the bite, deep enough to allow the escape of serum, and the third is mechanical suction to withdraw free venom. Experiments on dogs have shown that the common applications, such as potassium permanganate, kerosene or turpen- tine, are useless. Potassium permanganate oxidises and destroys the venom outside the body, but in the poisoned wound its local destructive action does more harm than can be balanced by the possible destruction of some unabsorbed venom. A review on the fatal cases empbasises the importance of early treatment under competent medical direction. In half the cases which eventually died there was delay of more than two hours before the first dose of antivenin was given. Antivenin gives prompt relief, and as long as the patient is alive there is a chance that it will counteract the poison. The Institute recommends as first-aid measures, the application of a tourniquet a few inches above the bite and an immediate subcutaneous injection of antivenin, supplemented by incision and suction if the bite has been inflicted by a large snake and if the symptoms are severe and develop rapidly. The victim is advised not to run or get hot. and to avoid 1 THE LANCET, Oct. 5th, p. 744, and Oct. 19th, p. 850.
Transcript

1102

Annotations.

THE OPTICAL PROPERTIES OF THE CEREBRO-

SPINAL FLUID.

"Ne quid nimis."

DURING the last 20 years the cerebro-spinal fluid has.provided a rich field for those who have the desire andability to search for the hidden things in the chemistryand physics of the body. The chief value of thisfluid from the point of view of research lies in theconstancy of its normal chemical and physical com-position, and in its comparative freedom from theproteins and protein compounds which complicatethe physico-chemical examination of the blood. SinceMestrezat settled the normal chemical composition ofthe fluid many investigators have examined the- relation of variations in this to variations in bloodchemistry with fruitful results. It may even be saidthat the chemistry of the cerebro-spinal fluid indisease has in many ways helped us to understand thechemistry of the blood. More recently the finermethods of the physical laboratory have been appliedto the cerebro-spinal fluid, partly from a pure desirefor knowledge, and partly in an attempt to find newmethods which will help in the diagnosis of disease.Electric properties, such as electro-conductivity andthe electric charge of the proteins, have already beenexamined, and now the optical properties of the fluid- are being investigated by modern instruments.Two recent papers deal with the refractility of the

fluid and its power of absorption of the ultra-violetend of the spectrum. Penfold and Price,1 who haveinvestigated the refractile properties of the fluid withthe Zeiss dipping refractometer, had the results ofseveral previous workers as a basis for their investiga-tions. It may be said at once that their results agree- closely with what had previously been found. Theyestablish the normal refractility at 1-33510 in the.-adult and 1-33508 in the child, with variations of nomore than six units in the fifth decimal place. Anygreater variation they have found to be pathological,and to indicate some disturbance either in the

- chemistry of the cerebro-spinal fluid alone or morecommonly in the chemistry of the blood. The chiefvalue of their work appears to lie in the correlationwhich they have sought and sometimes obtainedbetween the changes in the proportions of the chemical°constituents of the cerebro-spinal fluid and thealterations in refraction. Thus in nephritis anddiabetes the refractility as calculated from thechemical examination might be identical with thatobtained directly by the refractometer. When thisparallelism was not obtained it was considered that- some chemical substance which had not been investi-,gated in the routine examination was present inabnormal concentration, and a further examinationmight reveal this. In diseases of the central nervous,system there was often little departure from thenormal refractility, since an increase in proteinmight be compensated by a reduction in the chloridesor glucose. Increase of refractility was much more..common than reduction, and was the rule in many.diseases of the nervous system, such as cerebral and.,gpinal tumour. On the whole, however, the refrac-tometry of the cerebro-spinal fluid appeared to be ofmore clinical value in general diseases such as uraemia,and diabetes than in diseases confined to the central-nervous system.

The absorption of the ultra-violet end of thecopper arc spectrum has been studied by FretsonSkinner,2 who hoped to gain by this means someindication of the nature of the colloids present in thecerebro-spinal fluid. In this he was disappointed, for

1 Penfold, W. J., and Price, C. A. E.: Med. Jour. Australia,Sept. 28th, p. 424.

2 Skinner, F. Fretson: Jour. Neur. and Psycho-path., 1929,x., 97.

the absorption of ultra-violet rays appeared to haveno necessary relation to the colloids in the fluid. Norwere any characteristic bands observed. He did,however, find important variations from the normalin certain diseases. Thus tabes dorsalis con-

stantly caused an increased absorption at the ultra-violet end of the spectrum, general paralysis rathermore, and tuberculous meningitis much more. Somediseases, such as disseminated sclerosis, might, how-ever, give almost normal spectra. The number offluids examined and the exact spectrum given byeach is not stated. This method of examining thecerebro-spinal fluid is of some theoretical interest, butuntil the results which it gives can be correlated withchanges in the constituents of the fluid it is likely tobe of little practical value.

SNAKE-BITE AND ANTIVENIN.

SNAKE-BITE does occasionally, if rarely, give riseto alarming symptoms in this country, as our

correspondence columns recently testified.1 Our onlypoisonous snake is the adder, but in the United Statesof America rattlesnakes are responsible for themajority of cases, although the number of bites bycopper-heads exceeds those of any other one species.In the current Bulletin of the Antivenin Institute ofAmerica, R. H. Hutchison has collected 607 case

reports of snake-bite for the year 1928, and found thatthe species of snake could be identified with a fairdegree of accuracy in three-quarters of them. FromApril until July the risk of snake-bite increasessteadily, but it b(gins to decline again in the middle ofSeptember, and has practically ceased to exist by themiddle of October. The greatest danger seems to liein picking up or reaching for something on the ground.because any movement towards an unseen snake willelicit a lightning-like defensive bite. The symptomsvary considerably, but in most cases swelling and painappeared early, and were the outstanding features.If the bitten part did not hurt and swell, the snake waseither non-poisonous or its injection apparatus wasnot working properly. Other symptoms noticed wereweakness, giddiness, haemorrhage, difficulty in breath-ing, nausea and vomiting, as well as a host ofoccasional distuibances. The reports include almostevery conceivable method of treatment, from theapplication of a freshly killed chicken to cauterisation,and specific treatment with antivenin. From thisabundance of r c -)mmendations three first-aid methodshave emerged as having real value. The first is theapplication of a tourniquet above the bite, drawntightly enough to obstruct venous return. It shouldbe released every quarter of an hour for at least twominutes to re-establish the circulation, its purposebeing only to diminish the rate at which the venomenters the general circulation. The second measureis a crucial incision over the bite, deep enough toallow the escape of serum, and the third is mechanicalsuction to withdraw free venom. Experiments ondogs have shown that the common applications,such as potassium permanganate, kerosene or turpen-tine, are useless. Potassium permanganate oxidisesand destroys the venom outside the body, but in thepoisoned wound its local destructive action does moreharm than can be balanced by the possible destructionof some unabsorbed venom. A review on the fatalcases empbasises the importance of early treatmentunder competent medical direction. In half the caseswhich eventually died there was delay of more thantwo hours before the first dose of antivenin was given.Antivenin gives prompt relief, and as long as thepatient is alive there is a chance that it will counteractthe poison. The Institute recommends as first-aidmeasures, the application of a tourniquet a few inchesabove the bite and an immediate subcutaneous injectionof antivenin, supplemented by incision and suctionif the bite has been inflicted by a large snake and if thesymptoms are severe and develop rapidly. Thevictim is advised not to run or get hot. and to avoid

1 THE LANCET, Oct. 5th, p. 744, and Oct. 19th, p. 850.

1103

alcohol and cauterisation. The antivenin injectionshould be repeated every half hour unless and untilsymptoms are markedly reduced, and intramuscularinjection is better than subcutaneous ; while for casesnot seen until some time after the bite intravenousor, for small children, intraperitoneal injection isrecommended. Caffeine, strychnine, and intravenoussaline should be available where there is much shock.The Walter and Eliza Hall Institute of Research in

Melbourne is devoting a special grant from theCommonwealth department of health to researches onthe Australian snake venoms. Venom is beingcollected from a large number of snakes by makingthem bite through a fine piece of rubber stretchedacross a medicine glass. The death-rates from thecommon snakes in Australia are 50 per cent. from thedeath-adder, 40 per cent. from the tiger snake, and9 per cent. from the brown snake. Dr. K. D.Fairley has studied the results of intiavenous injec-tions of venom in sheep, and has found that theclotting-time of the blood is increased but that nointravascular clotting was caused. He has alsostudied the dentition and bite mechani m of thevenomous snakes, and places the death-adder firstand the brown snake last. In another paper heshows that a snake which has recently struck maystill be dangerous, for even after biting several timesit may still have an appreciable amount of venomleft in the gland. His experiments suggest that tiger-snake venom, after the natural bite, is absorbed intothe circulation in less than two minutes, so that ifligature and incision are to be effective they must beapplied within this time. The value of this methoddepends on a thermolabile constituent of the venom,for if the thrombase in the venom was destroyed byheating to 75° C., ligature only delayed and did notprevent death. On the whole, therefore, he does notthink that ligature is of very much use except todelay absorption, while the excision is being carriedout. Dr. C. H. Kellaway, director of the Institute,has described a new phenomenon in the action of thesnake venoms on isolated smooth muscle. Thereaction closely resembles the anaphylactic reaction ;the muscles can easily be desensitised, and one venomwill sensitise to others. The action of the venomappears to be on the muscle itself, and not on the endplate, and the desensitisation is permanent.

IRRADIATED MILK.

STANDARDISATION in the vitamin content of foodshas made an important step forward. On p. 1090 ofour present issue Miss K. H. Coward, D.Sc., makes acomparison between irradiated cow’s milk, and cod-liver oil as sources of vitamin D, and she is able to dothis accurately by comparing both with a standardsolution of irradiated ergosterol. She takes as

her standard the antirachitic power of one ten-thousandth of a milligramme (0-0001 mg.) of irradiatedergosterol and calls this one antirachitic unit. Thoughthis unit is not as yet universally adopted, its use iscertainly an important step in the right direction.Dr. Coward was able to demonstrate that the anti-rachitic value of the milk was very materiallyaugmented by a brief period of irradiation-30 secondsapproximately. Before irradiation the milk onlypossessed about one twenty-fifth of an antiraciiticunit per gramme ; after irradiation the value wasenhanced to one-fifth of a unit, and in some cases,differently irradiated, to two units per gramme. Thrsa child receiving a litre of milk daily would get theequivalent of 0-004 mg. of irradiated ergosterol in thenon-irradiated milk, while in the best irradiated milkthe equivalent would be 0-2 mg. The former amountwould probably be insignificant, but the latter mightbe adequate prophylactically, though probably notcuratively for an infant. The usual curative dosefor an infant is from 1 to 2 mg. Dr. Coward laysemphasis on the marked deficiency in antirachiticpotency of ordinary milk which has not been irradiated.On Oct. 5th we published a paper by Dr. ChalmersWatson and others in which some remarkably

successful cures of rickets with irradiated milk wererecorded. The amount of milk given was not verylarge, and for some reason it seems to have beeneffective in one case in which the specific antirachiticagent, irradiated ergosterol, is stated to have failed.On the other hand, II. Hentschel and A. RoszkowskPexpress themselves strongly against the use ofirradiated milk in the treatment of florid rickets,as compared with the use of irradiated ergosterol.If it could be ensured that irradiated milk, at noenhanced cost, would reach children who are nottouched by any other form of antirachitic prophy-laxis, it might have a considerable value ; but other-wise it seems undesirable that its use should replacethat of irradiated ergosterol, which is specific inthe treatment of rickets.

PATHOGENESIS OF CONGENITAL SYPHILIS.

THE poverty of the material at the disposal of theclinician and more especially the clinical teacherof to-day, as compared with that to which he hadaccess at the beginning of the century, has beenremarked upon by physicians when occasion hasled them to retrospect of their own experience.Sir Humphry Rolleston, in a remarkable addressto the Medical Society of London on changes in theclinical aspects of disease, drew attention to theincreased rarity of certain morbid conditions, due insome cases to the effects of treatment and in othersto variations in the virulence of infective agents.Dr. F. J. Poynton, in his presidential address to a.

section of the Royal Society of Medicine in the presentyear, reminded his hearers of the kind of materialthat presented itself to paediatrists of the time ofCheadle-material which at any rate in civilisedcountries will never be seen again. Since it may wellbe said that the greatest advances in preventive andcurative medicine have been made in connexion withdiseases of the young, it is likely that in these disordersespecially the material furnished by the past wassuperior to that of to-day. This fact. does not applyto the clinician alone, but exerts a considerable effecton the activities of the pathologist, almost alwayswith the result that he is driven to employ moreindirect methods of investigation, and that the exactstages and sequences of the morbid process are moredifficult to determine. No more striking testimonyto the existence of this state of affairs could be forth-coming than the recent appearance 2 of Dr. OlufThomsen’s pathological atlas of congenital syphilisin the foetus, a disorder which has to so great anextent been modified by antenatal supervision andspecific treatment. Dr. Thomsen has reproducedin a separate volume (with a short explanatorytext written in German) the illustrations taken fromhis comprehensive work on the subject published inDanish in 1912. He justifies this course by thestatement, which no one who has seen the materialwill be likely to challenge, that it would hardly bepossible to obtain a collection of specimens at thepresent date which would be in any way its equal.He has incorporated with these illustrations a reviewof the problems connected with the transmission ofsyphilis to the foetus, and discusses the evidence whichhas accumulated in the years since they first appeared,giving a lucid summary of his interpretation of thisevidence. In general, he has found little cause toalter the view which he formerly expressed, that theinfection of the foetus is a placental one, and that agerminal (paternal) one is a hypothesis unsupportedby evidence. Dr. Thomsen puts forward as factsof great significance that it has never been shown thatan ovum infected with the spirochaete is viable(lebensfähig), and that in all the material which heinvestigated he has failed to find definite histologicalevidence of syphilis in a foetus less than 5 months old.

1 Münch. med. Woch., 1929, lxxvi., 1423.2 Pathologisch-anatomische Veränderungen fiber die Con-

genitale Syphilis bei dem Foetus und dem neugeborenen Kind.Copenhagen: Levin and Munksgaard; Leipzig: Georg Thieme.


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