979

and in some cases even these lesions were absent.No macroscopic disease was evident in the spleen or otherorgans. (The. inoculum was approximately 0-5 mg.and the animals were sacrificed on the 86th day afterinoculation.) In our experience, guineapigs injected withmuch smaller inocula of the parent strains show extensivedisease in the usual organs within one month.

One of us (E. G.) is the holder of a Lasdon FoundationResearch Fellowship of University College, Dublin.

VINCENT C. BARRYD.Sc. N.U.I., F.R.I.C., F.I.C.I.

MICHAEL L. CONALTYM.B. N.U.I., D.P.H.ETHNA GAFFNEYM.Sc. N.U.I., Ph.D.

Laboratories of the MedicalResearch Council of Ireland,

Trinity College,Dublin

REFERENCES

Barnett, M., Bushby, S. R. M., Mitchison, D. A. (1953) Lancet,i, 314.

Fisher, M. W. (1948) Amer. Rev. Tuberc. 57, 58.— (1952) Ibid, 66, 626.

Knox, R. (1953) Lancet, i, 443.— King, M. B., Woodroffe, R. G. (1952) Ibid, ii, 854.

Mitchison, D. A. (1952) Ibid, p. 858.Steenken, W. jun., Meade, G. M., Wolinsky, E., Coates, E. O.

(1952) Amer. Rev. Tuberc. 65, 754.Williston, E. H., Youmans, G. P. (1949) Ibid, 59, 336.Youmans, A. S., Youmans, G. P. (1948) J. Bact. 56, 245.Zetterberg, B. (1949) Acta path. microbiol. scand. suppl. no. 82.

Medical Societies

BRITISH ORTHOPÆDIC ASSOCIATION

THE association’s spring meeting was held in Dublinon April 23-25 under the presidency of Sir REGINALDWATSON-JONES.

Transfusion of Blood, Plasma, and Plasma SubstitutesDr. W. E. R. HACKETT (Dublin) discussed the advantages

of transfusions of blood, plasma, and plasma substitutesbefore and during surgical operations. In ansemic patientswho required transfusion before operation it was importantthat the blood be given several days beforehand so thatthe body might benefit as fully as possible. Blood givenduring operation had its greatest usefulness in replacingblood lost: this was often more than was realised. A commonunsuspected source of blood-loss was bleeding into the tissues,and this was an important cause of oligsemic shock afterinjuries such as fractures and extensive limb wounds. Therisks of overloading the circulation by over-transfusionwere small ; a commoner error was not to give enough blood.With expert laboratory help reactions from mismatchingwere exceptional ; mistakes, when they occurred, were

more often due to clerical errors or confusion of patients withsimilar names than to mistakes in grouping. In practice theonly rhesus factor of real importance was the D antigen.So far there was no true substitute for blood. So-calledblood substitutes were really plasma substitutes, and nonewas equal to plasma itself. A perfect plasma substitutemust have the same osmotic properties as plasma ; this was

very difficult to achieve. The best types at present availablewere the polyvinyl polymers such as ’ Plasmosan ’ and thesugar polymers such as dextran.

Ocular TorticollisProf. L. E. WERNER (Dublin) recalled the significance of

imbalance of the ocular muscles as a cause of tilting of thehead in infants and young children. When due to an ocularimbalance, such tilting could be corrected by an equalisingoperation on the eye muscles, though in long-standing casesthere might be secondary contractures of the neck muscles.Professor Werner classified torticollis as (1) purely ocular,(2) purely cervical, or (3) combined. From the orthopaedicpoint of view it was necessary to determine as soon as possiblein every case of torticollis whether there was an ocular elementin the deformity, if necessary by referring the patient toan orthoptic clinic. If an ocular defect was overlookedorthopaedic treatment directed to the neck would not becompletely successful.

Fracture of Head of RadiusMr. J. C. CHERRY (Dublin) had replaced the fractured

radial head by an acrylic prosthesis in selected cases in

which the head was badly comminuted. Mr. C. C. JEFFERY

(Exeter) believed that the operation had a definite place,especially in cases of fracture where the radial shaft was

displaced upwards ; such fractures were, however, exceptional.Prof. BRYAN McFARLAND (Liverpool) had found no tendencyfor the radial shaft to migrate upwards, even when the radialhead had been excised in children. Mr. ST. C. STRANGE(Canterbury) recalled that the position of the radius dependedupon the integrity of the interosseous membrane. If thiswas torn by the force of the injury the radius was displaced,but if the membrane remained intact displacement was notto be feared. Mr. PHILIP WiijES (London) thought that itwas necessary to know the late results of prosthetic replace-ment before determining the place of the operation. Mr.ARTHUR CHANCE (Dublin) believed that the radius mightmove upwards when weight was put on the wrist (e.g., leaningon a table) even though it appeared in normal position inroutine radiographs. There was an established place for theoperation, but if the capitulum was found to be badlydamaged at operation acrylic replacement was better avoided.Sir REGINALD WATSON-JONES (London) had no doubt thatthe operation was appropriate for the rare but definite casesin which fracture of the radial head was associated with

rupture of the interosseous membrane and marked upwarddisplacement of the radius.

Treatment of Club-footMr. A. T. FRipr (London) discussed the treatment of relapsed

or neglected congenital club-foot in children aged six monthsto ten years. In the past four years he had given an exten-sive trial to the Kite technique in which wedged plastersare used, and he had been impressed by the results. The

technique aimed at gradual correction without harmful forceand without anaesthesia. Each of the four components ofthe deformity (varus, inversion, equinus, and plantaris)was corrected successively by removing appropriate wedgesfrom the plaster and closing the gap, the adjustments beingmade weekly. During treatment the foot became progresivelymore supple, and in most cases satisfactory correction wasobtained. Professor McFARLAND agreed wholeheartedlywith the principle of gradual correction without the use offorce. Such a method reduced, though it did not eliminate,the necessity for operation.

Pott’s ParaplegiaMr. H. J. SEDDON (London) remarked that in paraplegia

of early onset the cord might be involved by an inflammatorylesion (fluid or solid), rarely by thrombosis of the vessels,and sometimes by mechanical collapse of the spine. Paraplegiaof late onset was associated either with an inflammatoryprocess or with pronounced bony deformity. The cordchanges in paraplegia were of four kinds : simple compression,infective thrombosis, pachymeningitis (rare), and longitudinalshrinkage. With conservative treatment alone paraplegiaof early onset persisted in about a quarter of all cases, andparaplegia of late onset in over half the cases. Operativetreatment offered a good prospect of mechanical relief :fluid pus could be drained by costotransversectomy, but solidmatter interfering with the cord was best removed by antero-lateral decompression (except in the neck and in certainlumbar lesions, where laminectomy offered advantages).Operation was indicated : (1) when paralysis had becomecomplete ; (2) in all cases of late onset ; (3) if continuedimprovement was not taking place under conservative treat-ment ; (4) when paraplegia was associated with uncontroll.able spasms of the legs ; and (5) if paraplegia recurred afterinitial recovery. In older patients operation should beconsidered relatively early. In cases with a visible abscessshadow costotransversectomy should be tried first, but if thiswas unsuccessful anterolateral decompression should beundertaken.

Mr. D. LLOYD GRIFFITHS (Manchester) described the

operation of anterolateral decompression employed byMr. Seddon, Mr. R. Roaf, and himself. He emphasised thatoperation was not required in every case of paraplegia.It was a difficult, formidable, and hazardous operation andpatients should not be submitted to it unnecessarily.Mr. Griffiths summarised the combined results in 48 patientsoperated upon by Mr. Seddon, Mr. Roaf, or himself. 34recovered enough to walk normally ; 11 recovered little ornot at all ; and 3 died. In successful cases recovery wasoften dramatic. Results were better in early cases with activedisease than in late cases with much bony deformity. Spinalfusion was always advisable after anterolateral decompression.

980

Mr. F. W. HOLDSWORTH (Sheffield) said that with the intro-duction of anterolateral decompression our ideas on thetreatment of Pott’s paraplegia had been revolutionised. Opera-tion seemed strongly indicated in any case where recoverywas not occurring with conservative treatment. Antibioticshad helped to make operation safer. Mr. NORMAN CAPENER(Exeter) suggested that operation should not be undertakenlightly. The operation he described was essentially the sameas that recommended by Mr. Griffiths, but he thought it

unnecessary to remove more than one or two ribs. Mr. J.DOBSON (Wrightington) thought that anterolateral decom-

pression should be done only in specially equipped centres.He emphasised the importance of treating the tuberculouspatient as a whole by constitutional measures. Mr.,R. W.BUTLER (Cambridge) believed that anterolateral decom-

pression would greatly shorten the duration of paraplegiaand would permit recovery in many patients who would nototherwise recover.

Treatment of Early PoliomyelitisSir HARRY PLATT (Manchester) remarked that a generation

ago outbreaks of poliomyelitis were always small and childrenwere almost exclusively affected. The main problem wasto prevent and relieve crippling deformity. As a result ofthe greatly increased incidence of poliomyelitis and the

frequent affection of adults, the subject had become even moreimportant. The prevention of deformity was still one of themain problems. This could be tackled efficiently by theorthopaedic surgeon only if the patient came under his careat an early stage. There was unfortunately a tendency forpatients to be brought too late to the orthopaedic surgeon.

Mr. D. M. BROOKS (London) outlined a programme oftreatment for patients with poliomyelitis. He recalledthat the aims of treatment, were to save life, to preventdeformity, to restore function, and to rehabilitate the patient.The orthopaedic surgeon should have access to the patientat an early stage, and he should have a full knowledge of thecomplications that endangered life and of their management,including the use of different types of respirator. In prevent-ing deformity the surgeon must remember its two causes

-faulty posture and muscle imbalance. Faulty posture,which might be assumed in an attempt to minimise pain,was always preventable by appropriate splints. Muscleimbalance was more difficult to counteract, especially inchildren ; when this was great, it was impossible to preventdeformity simply by external retentive apparatus. Relativelyearly tendon transplantation was often necessary. Activeuse of recovering muscles should be encouraged with relativecaution ; fatigue might be harmful during the early months.Electrical muscle tests were of value in determining at anearly stage whether paralysis was going to be permanent.In general, if a muscle showed no sign of recovery withinthree months it was unlikely ever to recover. This knowledgeenabled an early decision to be made on the question oftendon transplantation. Mr. H. H. LANGSTON (Winchester)said that it was important that the orthopaedic surgeonshould have early access to patients with poliomyelitis. Therewas a tendency for too much delay. Professor McFARLANDbelieved that early orthopaedic management would best besecured by the efforts of individual orthopaedic surgeonsin their own areas. Mr. R. I. STIRLING (Edinburgh) suggestedthat in time of epidemics blocks of beds in fever hospitalsshould be put at the disposal of the orthopaedic surgeons,who otherwise might be unable to accommodate the largenumbers of cases in their own wards. Mr. J. C. SCOTT (Oxford)believed that in the early stages the ideal arrangement wasclose cooperation between orthopaedic surgeons, paediatricians,and infectious-disease physicians. Orthopaedic surgeons shouldstrive to contribute more to the solution of problems of theearly phases of the disease.

Dupuytren’s ContractureMr. J. I. P. JAMES (London) recognised contracture of the

fifth finger as a distinct clinical type in which the distal

interphalangeal joint was not uncommonly flexed. Hehad found " knuckle pads " associated with Dupuytren’scontracture in nearly a quarter of all his cases ; the micro-scopic appearance of the pads was similar to that of thepalmar fascia. Plant,ar involvement was also common.

In the elderly subcutaneous tonotomy was occasionallyjustified, but for the ordinary case excision of the palmarfascia through a skin-crease palmar. incision and throughinidlateral digital incisions was recommended. The greatest

hazard was eedema of the hand. Of 84 cases reviewed theresult was perfect or good in 64, and fair or poor in 20. Meta-

carpophalangeal Contracturos could usually be overcome,whereas interphalangeal contractures were very liable to

persist.Amputation of all Toes

Mr. K. I. NISSEN (London) said that there was a place foramputation of all the toes in cases of gross deformity withrigid, functionless, but painful toes. Such a condition most

commonly followed " burnt-out " rheumatoid arthritis ;occasionally it was induced by peroneal muscular atrophyor by frostbite. The nature of the proposed operation shouldalways be clearly impressed on the patient, whose writtenpermission should be secured. After operation it was oftenpossible for ordinary shoes to be worn, but special shoes mightbe required.

Tendon Transplants for Claw-toesMr. R. G. TAYLOR (Oxford) had studied the results, in 68

patients, of Girdlestone’s operation of transplantation of thelong too-flexors into the extensor expansion. for claw-toes,The results were almost uniformly good.

Colles FractureMr. W. DOOLIN (Dublin) sketched the background against

which Abraham Colles occupied with distinction the chairof surgery in Dublin. Colles was a man of exceptionalmodesty, admired by his colleagues and by students alike forhis upright character and intense honesty.

Mr. G. N. GOLDEN (Guildford) had studied the late resultsin 110 cases of Colles fracture treated one to twenty yearsbefore. Most fractures had been treated by junior residents,and the usual method had been manipulative reduction andimmobilisation in plaster for four weeks. 15 fractures had

required remanipulation for secondary displacement. Resultswere assessed on the basis of pain, functional disability,and deformity. Mr. Golden concluded that age alone was notan important factor in the result. The type of fracture wasof some significance, the frequency of poor results beinggreater after comminuted fractures and especially afterfractures complicated by radio-ulnar subluxation. Therewas a definite and striking relationship between the qualityof’ the reduction maintained and the result. More stablereduction, and consequently improved results, might followthe use of above-elbow plasters. Dr. W. R. HARRIS (Toronto)said that one of the difficulties was to maintain reduction.He and his colleagues in Toronto believed that the use ofplaster-of-paris was an inefficient method, especially incomminuted fractures. In selected patients a trial had beengiven to mechanical fixation by pin units of the Roger Ander-son type. In 23 cases observed for from two months to five

years after treatment there had been no recurrence of deformityand no patient had lost more than 5° of wrist movement.In 2 cases the pin fixation had -to be abandaoned becauseof pin-track infection.

Median-nerve Compression in the Carpal TuimelMr. J. S. R. GoLDING (London) recalled that pain and

tingling in the distribution of the median nerve in the handwere commonly due to compression of the median nervebehind the transverse carpal ligament. He had studied theclinical features and results in 50 patients subjected to opera-tion. Most patients were women in middle life, and in halfthe symptoms were bilateral. Tingling at night was pro-minent, and was often relieved by hanging the arm out ofbed or shaking it. There was usually impairment of sensa-tion, and sometimes there were motor weakness and wasting,which might be confined to the abductor pollicis brevisand opponens pollicis. The causes of the narrowing of thetunnel fell into two groups-non-traumatic and traumatic.Non-traumatic conditions included ganglion, tenosynovitis.changes in the transverse ligarnent itself (acromegaly, Leri’spleonosteosis), and idiopathic. The traumatic group includedearly lesions such as hsematoma, carpal dislocation, andfractures with displaced fragments, and late lesions such asold fractured scaphoid and gross traumatic arthritis. Theresults of decompression by division of the transverse carpalligament were good. The symptoms were almost alwaysrelieved. There was usually good or moderate recovery ofsensibility, but motor impairment often persisted.

Edward Hallaran BennettMr. W. GrssANE (Birmingham) paid a tribute to the

memory of Edward Hallaran Bennett (1837-1907), a former

981

professor of surgery in Dublin who described the injurynow widely known as Bennett’s fracture. Mr. Gissane saidthat the injury was, now believed to be an adduction injury,and added that, although it might be reduced clinicallywithout difficulty (as had been claimed by Bennett before thedays of X rays), it was essential to maintain reduction underclose radiographic control. Operative suture of the rupturedjoint capsule might be required to prevent redisplacement ;and, when necessary, this should be done early while thedamaged tissues were still recognisable and easily handled.For late disability after inadequate reduction arthrodesiswas preferable to arthroplasty.

1. See J. biol. Chem. 1953, 200, 89.

AMERICAN ASSOCIATION FOR CANCER

RESEARCH

THE forty-fourth annual meeting of the associationwas held in Chicago from April 9 to 11.

Tobacco CarcinogensE. L. WYNDER, E. A. GRAHAM, and A. B. CRONINGER

(St. Louis and New York) reported studies on the carcino-genicity of tobacco tars. Smoke from cigarettes, smokedin a. manner simulating human smoking habits, was condensedin flasks immersed in dry ice and ethyl alcohol, and the

resulting tars dissolved in acetone. One out of every twomice painted with this solution developed a papilloma, theearliest tumour appearing after 8 months ; the average time

required was 13 months. A carcinoma developed in one outof every six mice, the earliest after 10 months, and the averagetime of induction was 15 months. Some of these carcinomasmetastasised to the lungs, and some were successfully trans-planted for several generations. No tumours developed inthe control mice painted with acetone alone.

Cancer of the CervixC. C. ERICKSON and his associates (Memphis, Tennessee)

gave a preliminary report of the results of cancer screeningof the general population : 20,000 women were examined bythe vaginal-smear technique, and suspicious and positivesmears were found in about 1-8% of women examined.

Subsequent biopsies showed that about half of these womenhad intra-epithelial carcinoma of the cervix or invasive cancer.

S. C. KASDON and W. H. FISHMAN (Boston) reported workdone since 1951 on the &bgr;-glucoronidase activity of the vaginalfluid of 386 cancer-free premenopausal women*: 88-6% hadvalues below 400 units per g. Of the remaining 11-4%, themajority had gynaecological disorders such as preclinicalcancer of the cervix, gonococcal and other infections, andovarian dysfunction. Only 3 out of 16 premenopausal womenwith untreated primary invasive epidermoid cancer of thecervix showed vaginal-fluid &bgr;-glucoronidase activity below400 units per g. But high vaginal-fluid &bgr;-glucoronidase levelswere often found in postmenopausal women and in thosewith deficient ovarian function who showed no clinical orother evidence of cancer.

Hydatid MoleRoy HERTZ (Bethesda, Maryland) reported the absence .of

histidinuria of pregnancy in patients with hydatid mole,although high urinary gonadotrophin titres were found. Ascortisone and A.C.T.H., but not progesterone, have been saidto produce definite histidinuria, its absence in cases of hydatidmole may reflect a change in adrenal function. This deviationfrom the normal urinary findings in pregnancy may be auseful test for hydatid mole.

Cancer of the ProstateW. H. FISHMAN, F. LERNER, and F. HOMBURGER (Boston)

reported a method for estimating serum-acid-phosphatase ofprostatic origin, which depended on the ability of l-tartrateto inhibit prostatic-gland acid. phosphatase.! 1 This " pros-tatic aoid-phosphatase constituted 10-30% of the totalserum-acid-phosphatase. In cases of disseminated prostaticcancer abnormal serum levels of this fraction were commonerthan abnormal conventional acid-phosphatase levels. Somemen, with normal conventional serum-acid-phosphatase andabnormal "

prostatic " serum-acid-phosphatase were subse-quently found to have cancer of the prostate, though therewas no radiological evidence of bone metastases at the timeof the phosphatase estimations.

Leukaemia -

A. J. ANLYAN (New York) had studied the &bgr;-glucoronidaseactivity of the leucocytes of 46 leukaemic children under13 years of age. The leukaemia was predominantly a

" stem-cell leukaemia." The patients were divided arbitrarily intothree groups : those with leucocyte enzyme activity below2000 units per g. of buffy coat ; those with between 2000and 4000 units ; and those with over 4000 units. Thepatients were equally divided among the three groups. Itwas found that the first group responded well to treatment,though the remissions were short and could seldom beachieved twice. The second group included many of the

patients that survived a year or more and who had longerremissions than the other groups. The third group pursueda rapidly fatal course despite treatment.

Metastatic Tumours of Bone

JUDITH BELLIN, AGNES HAUSINGER, and HERTA SPENCER(New York) described experiments on the metabolism andremoval of radiocalcium (Ca45) in patients with osteolyticor osteoblastic metastases. Tracer doses were injectedintravenously. The loss of Ca45 through the alimentarytract was similar in both groups, but the urinary excretionwas 60-80 times greater in patients with osteolytic metastasesthan in those with osteoblastic metastases.

Tumour Growth

0. H. PEARSON and C. D. WEST (New York) discussedobjective methods for the measurement of tumour growth inman. Lymphoid tumours and the myeloid tissue of acuteleukaemia contained three times as much phosphorus per unitof nitrogen as muscle tissue, and thus growth or destructionof such tumours should be accompanied by a positive ornegative balance of these elements in the same ratio as theyexist in the tumour tissue. Slight changes in tumour massof approximately 30 g. wet weight of tissue per day weredetected in this way. Further, osteolytic tumours grow bydestroying normal bone ; it was assumed that growth of1 g. of tumour caused destruction of 1 g. of bone, and hencea negative calcium balance of approximately 150 mg. ; thisamount of calcium loss per day was readily measured.

ChemotherapyA new substance, 6-mercaptopurine, has recently been

intensively studied at the Sloan-Kettering Institute foiCancer Research, New York. Some preliminary exparimentaland clinical results were presented by workers at the institute.D. A. CLARKE and his associates reported that this substancewas a unique inhibitor of the transplantable mouse tumour,sarcoma 180. It was effective orally or parenterally. Atfirst there was only moderate inhibition of tumour growth,but later most tumours became non-viable-i.e., unable to" take " when transplanted to normal mice. Survival-timewas increased in treated mice and there was complete regressionof the tumour in a significant number. J. H. BTJBCHEJSTALand his group gave details of some preliminary trials in over100 patients with advanced neoplastic disease. The usualoral dose was 2-5 mg. per kg. body-weight until a therapeuticeffect or a fall in the total leucocyte-count appeared. Childrentolerated this dosage level for a longer period than adults.Particular caution was needed in patients with impairedrenal function or very high leucocyte-counts, for difficultiesin uric-acid excretion occurred when tissue breakdown wastoo rapid. The main toxic sign was depression of the blood-count, but marrow examination showed none of the morpho-logical changes characteristic of intoxication with folic-acidantagonists. 14 out of 45 children with acute leukaemiawere temporarily improved, and 11 showed substantial

improvement.A. GELLHORN and his colleagues (New York) described

laboratory and clinical studies of 1 : 4-dimethanesulphonyl-oxybutane (‘ Myleran ’). This was a potent carcinostatic

agent for the mouse mammary tumours 755 and E 0771,and for the Brown-Pearce carcinoma in rabbits. Clinically,they had confirmed recent observations 2 3 that the drugwas useful in the management of chronic myeloid leukaemia.

S. FARBER and his colleagues (Boston) discussed the anti-metabolite, antimalarial, and anti-cancer activity of a seriesof new dihydrotriazines. The monoehlor and the dichlor

compounds showed a definite but temporary effect in childrenwith acute leukaemia resistant to folic-acid antagonists,

2. Haddow, A., Timms, G. M. Lancet, Jan. 31, 1953, p. 207.3. Galton, D. A. G. Ibid, p. 208.