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Annotations

SURGICAL TREATMENT OF PAIN

THE study of the anatomy and physiology of pain hasmade remarkable progress in the last ten years, especiallyin this country under such prominent workers as SirThomas Lewis and H. H. Woollard, and in America,where H. G. Wolff,l by ingenious but fairly simplemethods, has lately unravelled the puzzling mechanismof headache in a variety of clinical conditions. Nosimilar progress has been made in the art of relieving thesymptom. The general and local anaesthetics dispelpain nonspecifically by abolishing all forms bf sensation.Morphine is more specific, as are the new drugs, such aspethidine, which are intended to replace it ; but theycarry the grave risk of addiction. With recurrent or

persistent pain, as in trigeminal neuralgia and tabeticcrises, the physician now calls on the surgeon to blockor cut the pathways of pain sensation at one or severallevels, but often this surgical treatment does not producethe expected relief, perhaps because of the subjectivenature of the symptom. Psychologists have always founddifficulty in classifying it as either a sensation or an

emotion. Like other sensations, it has a threshold andcan be localised and referred to a stimulus ; but it isinterpreted much closer to the centre of personality thanother sensations, such as touch and hearing, and it hasmuch in common with emotions like fear and disgust.Workers in sensory physiology have often tried to differ-entiate the sensory component from the " unpleasantness

"

or " reaction to pain " of the emotional element, which they

have left to the consideration of the psychologist.2The futility of dualistic classifications of pain is

illustrated by the observations of Professor Freeman andDr. Watts, published in our last issue. After observingin psychotic and neurotic patients the relief of " mentalpain " by prefrontal leucotomy (the Americans preferto call it lobotomy), they have attacked the emotionalcomponent where its appreciation is linked with thecentre of personality-the frontal -lobes. Logically, thisis correct ; but some of their examples provide little

support for the operation because of the patient’s hope-less or terminal condition at the time of operation andbecause of the admixture of psychiatric symptoms.By some it may be regretted that now, when the psychò-logical aspect of somatic symptoms -in general medicineis being increasingly recognised and understood, the

neurosurgeon has stepped forward in readiness to dealwith one of these symptoms. It would, however, bewrong to think that all psychological symptoms can betreated by psychotherapy alone. For the patient withsevere hypochondriasis and crippling pain which isuncontrolled by psychological or physical methods,prefrontal leucotomy deserves consideration.

RUTIN FOR INCREASED CAPILLARY FRAGILITY

BOTANICAL sources for drugs influencing .haemorrhageseem of peculiar interest to American pharmacologists ;after spoiled sweet clover as a source of dicoumarin,buckwheat as a source of rutin is proposed. Rutin hasbeen used by Shanno 3 for the treatment of haemorrhagedue to increased capillary fragility. It is a crystallineglucoside that was isolated as long ago as 1860 bySchunck at Manchester, and it can be obtained in a reason-ably pure state by recrystallisation. The rationale ofits use for influencing capillary fragility is briefly as

follows : Szent-Gyorgi separated from impure naturalvitamin C a substance that, experimentally, correctedincreased capillary fragility in guineapigs ; this substancehe called " citrin," or vitamin P ; later, citrin was shownto be an impure mixture of two flavone glucosides,

1. Wolff, H. G. Arch. Neurol. Psychiat. 1943, 50, 224.2. Guttman, E., Mayer-Gross, W. Lancet, 1943, i, 225.3. Shanno, R. L. Amer. J. med. Sci. 1946, 211, 539.

hesperidin and eriodictyol. (Neither of these glucosides,however, gave really satisfactory results ; hesperidinhas been the more extensively tested, but the resultshardly aroused any enthusiasm.) Rutin is a flavonederivative with a chemical structure similar to hesperidin,and the possibility that this was the active substance inthe citrin mixture led to these trials.For testing, Shanno used Gothlin’s technique of

estimating capillary fragility : this consists in countingthe petechiae produced in a circle 6 cm. in diameter onthe antecubital fossa below a blood-pressure cuff inflatedto 35 mm. Hg for 15 min., and repeated, an hour later,at 50 mm. Hg. The dose of rutin was 60-120 mg. dailyby mouth. A group of 24 hypertensive patients wastested. Thirteen of them, with hypertension andincreased capillary fragility, showed a return to normalGothlin fragility on rutin treatment. Of 11 hyper-tensive patients receiving thiocyanate treatment, 7 hadnormal fragility and maintained it when given rutin

together with thiocyanate.; 3 had developed increasedfragility during treatment with thiocyanate, and rutinrestored it to normal ; 1, who had been given rutin forincreased fragility and become normal, was subsequentlygiven thiocyanate and rutin without relapse. Otherconditions treated were : 2 cases of haemorrhage fromthe respiratory tract for which no local lesion could befound, associated with increased capillary fragility, bothof which cleared up with rutin treatment for someweeks ; a case of thrombocytopenic purpura, unaffectedby rutin ; 3 cases of haemorrhages due to drugs (sulpha-diazine, gold, and aspirin), whose bleeding ceased withrutin treatment coupled with withdrawal of the offendingdrugs-a finding of doubtful value. Couch, Naghski,and Krewson 4 have investigated various plant sources ofrutin and find that buckwheat, leaves and blossom, givesthe best yield ; they report the conditions of croppingand preserving for obtaining the best results.

Haemorrhagic diseases associated with increasedcapillary fragility, as opposed to those due primarily todisturbance of platelet formation or the blood-coagulationmechanism, still present an intractable therapeuticproblem ; we hope that more detailed reports of the valueof rutin will support these preliminary investigations.

YEAR’S WORK AT THE LISTER INSTITUTE

THE report 5 of the Lister Institute for 1945-46 lists avariety of investigations on pathological, biochemical,biophysical, and nutritional subjects. Work has con-tinued on the alpha-toxin (lecithinase) of Clostridiumwelchii and on the pathogenesis of gas-gangrene. It hasbeen shown that lecithin occurs in the contractile elementof muscle, and this is of interest because of the earlyloss of contractility in muscle affected by gas-gangrene.Bacterial hyaluronidase, it appears, may consist of severalenzymes, and this may have important effects on theability of micro-organisms to attack and invade theanimal body. Study continues on the nuclear structuresof bacteria, on pyrogenic substances in materials used fortransfusion, and on the immunology of trichomonasinfections in cattle. -On the biochemical side there hasbeen progress in the study of human specific blood-groupsubstances and the specific group 0 substance has beenisolated. The structural chemistry of

"

gramicidin S "

has been investigated and a tentative formula suggested.A fresh approach is planned in seeking the nature of thesomatic antigens of gram-negative bacteria, and thesearch for better antitoxins goes on. In the biophysicalsection an attempt is being made to obtain a standardfibrinogen preparation for the assay of thrombin, andamong the practical problems solved is the supply offibrinogen, fibrin, and thrombin for the clinician. There

4. Couch, J. F., Naghski, J., Krewson, C. F. Science, 1946, 103,197.

5. Report of the governing body. Lister Institute of PreventiveMedicine, Chelsea Bridge Road, London, S.W.1.

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is much to learn about the nutritive value of differentfood proteins, and it is encouraging to find that the

proportion of the ingested nitrogen which becomesfinally incorporated in the tissues of growing animals isincreased from 23 to 27% as the degree of extraction offlour is raised from 70 to 100%. The nutritive value of

protein hydrolysates and of milk substitutes for use asinfant foods has also received attention, as have biologicalestimations of vitamins. These are a few of the usefulfindings published in some thirty papers during the year,and there is good reason for the feeling of the chairmanof the governing body that the institute is well embarkedon a career of new and expanding service to science andto the community.

IMMUNISATION WITH THE VOLE BACILLUS

THE vole bacillus, or the murine type of tuberclebacillus, occurs as a natural pathogen in some of the wildmice of Britain. It was first described by Wells 1 in1937, when he wa,s collaborating with Elton in a study ofthe- diseases of voles in Great Britain. Tuberculosis involes is a widespread disease, and is the only known

instance of tuberculosis affecting wild animals in theirnatural habitat. The type of tubercle bacillus causingtuberculosis in voles is not pathogenic to the usuallaboratory animals, the infection caused by the inocu-lation of the bacillus being transitory. This led Wellsand Brooke 2 to investigate the question whether inocu-lation of guineapigs with the vole bacillus increasedtheir resistance to subsequent infection with the humanor bovine types of tubercle bacillus. Their experimentswere interrupted at the outbreak of war and the animalshad to be killed. At that stage of the experiment theyconcluded that vaccination of guineapigs with the volebacillus gives a degree of protection against subsequentinfection with virulent mammalian tubercle bacilli whichis apparently far greater than has been recorded by othermeans.

The immunisation experiments in guineapigs have beenrepeated by several workers (Griffith and Dalling 3, inthis country, Irwin and O’Connell 4 in Canada, Wahlgrenet al. in Sweden, Corper and Cohn 6 is America, andBirkhaug in Norway). The methods employed di ffer

widely, but all agree that a pronounced increase of resis-tance to infection with virulent tubercle bacilli followsinoculation with the vole bacillus. It. is quite clear,however, that in the guineapig resistance does notamount to immunity. The effect of inoculation is a

delay, often very considerable, in the establishment of :

generalised disease after infection with virulent tuberclebacilli, but death from tuberculosis eventually follows.The painstaking work of Birkhaug makes this abundantly i

clear. The average survival time of twelve unvaccinated 1

guineapigs after infection with virulent tubercle bacilli 4

was 192 days, whereas that of twelve animals vaccinatedwith the vole bacillus before infection was 403 days. i

It is still uncertain how the resistance conferred on 1

guineapigs by vaccination with the vole bacillus compareswith that produced by B.C.G. The results of Wells and 1Brooke, of Irwin and O’Connell, and of Wahlgren and icolleagues, suggest that in the earlier stages of artificial 1infection vaccination With the vole bacillus produces Ithe greater resistance. Corper and Cohn, and Birkhaug, I

on the other hand, have found that the resistance con- 7ferred is about equal, if the animals are allowed to fsurvive. It is very doubtful if immunity experiments iin tuberculosis in the guineapig can be translated into Iterms of human immunity. The guineapig is absolutely isusceptible to infection with mammalian tubercle bacilli fand shows no natural resistance to progressive infection. t1. Wells, A. Q. Lancet, 1937, i, 1221.2. Wells, A. Q., Brooke, W. S. Brit. J. exp. Path. 1940, 21, 104.3. Griffith, A. S., Dalling, T. J. Hyg., Camb. 1940, 40, 673.4. Irwin, D., O’Connell, D. C. Canad. med. Ass. J. 1943, 48, 486.5. Wahlgren, F., Olin, G., Widström, G. Nord. Med. 1944, 22, 943.6. Corper, H. J., Cohn, M. L. Amer. J. clin. Path. 1943, 13, 18.7. Birkhaug, K. Amer. Rev. Tuberc. 1946, 53, 411.

In man, natural resistance, or resistance acquired as aresult of previous infection, can completely overcome atuberculous infection. In other words, infection in theguineapig is inevitably fatal ; whereas the result in man isdetermined by the balance between natural or acquiredresistance and the infective process. An increase inresistance in man may lead to healing of the infection ;an increase in resistance in the guineapig merely delaysits death.There are several questions still to be answered beforethe vole bacillus can be considered for human vaccination.Is it incapable of producing progressive disease in man ?Will it convert a negative reactor to tuberculin into apositive reactor, and how long does this sensitivity last ? YCan human vaccination with the vole bacillus be donewithout causing severe local or general reaction ? Y Doeshuman vaccination confer increased resistance to tubercu-losis It is hoped that the first three questions may soonbe answered. The last question is vital, but the answermay be delayed for some time. Evidence of this natureis notoriously difficult to collect, and careful planningwill be needed if the answer is not to be indefinitelypostponed.BICENTENARY OF THE LONDON LOCK HOSPITALAT the time the London Lock Hospital was founded

200 years ago, there were two ancient lock hospitalsstill functioning in London-all that remained of theseven lazar-houses granted to St. Bartholomew’s Hos-

pital by Henry vm at the time of the dissolution of themonasteries.

Locks, lazars, or outhouses were a recognised featureof the medieval hospital system of England. Theywere built by the pious especially for the treatment oflepers, because these outcasts were not admitted tothe buildings attached to the monasteries reserved forthe sick, the halt, and the blind. Instead, for them,wandering along the highways of medieval Englandwith their begging-bowls and rattles, special lazar-houses were erected close to the monastery gates ; andthere -at sundown the real lepers as well as the mencovered with the foul ulcers of untreated scabies, thevictims of lupus and rodent ulcer-all loosely diagnosedas lepers-were segregated. Outside the lazars, basketsof rags, lint, or wool were placed so that the lepers mightwipe their sores before admission. The baskets wereles loques (French for rags) and the lazars in NormanEngland came to be known as les locks. But whenleprosy declined in Europe, and especially in England,towards the end of the 15th century, the lazar-housesbecame almost empty ; and it was then as it happenedthat syphilis burst upon an unprepared world. Naturallythe lazars were hastily turned over to the treatmentof venereal disease ; and the few remaining leperswere quickly swamped by the victims of syphilis. Itis believed that it was in this way the word " lockbecame associated with venereal disease.

Certainly there is no doubt that the hospitals for

lepers became hospitals for venereal disease. Up to 1813,for instance, there was a plaque on a tumbledownbuilding in Southwark labelled " The Chapel of thehospital for lepers, Le Lock, dedicated to St. Maryand St. Leonard. Founded prior to the 14th year ofEdward n." This belonged to the old lock hospitalfor men in Kent Street, vacated by St. Bartholomew’sin 1760 after 2t centuries of use as a venereal hospital.It was returning from this hospital that Percivall Pottis said to have broken his leg, for the surgeons ofSt. Bartholomew’s were surgeons to Le Lock from thetime of Thomas Vicarv until its extinction. It was

possibly the knowledge that the lock hospital in KentStreet and the " spital" for women in Kingsland wereabout to be done away with, coupled with the greatincrease in venereal diseases in outer London, thatinduced William Bromfeild (1713-92), surgeon to St.