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exaggerated insulin responses to glucose, and whichis manifested by diminished effects of exogenousinsulin on glucose uptake in the forearm.21,22The abnormalities in the concentrations of in-

dividual aminoacids in the blood of obese subjectsare not great, and it is not known whether com-

parable changes provoked by exogenous acids givensingly or in combination are capable of sustainedstimulation of insulin secretion. Although the systemwhich maintains the blood level of I.R.I. is exquisitelysensitive to the administration of arginine, which isknown to be the most potent of the aminoacids in this

respect, the response to parenteral infusions of theaminoacid is only transient when doses are small. 23It is possible that raised blood levels of endogenousmetabolites are not equivalent, as stimuli, to the samelevels attained with exogenous materials, since theiractions presumably depend on processes involvedin the metabolic fates of the agents, which might differin these two situations. The factors that regulate theblood levels of individual aminoacids are ill under-

stood, but they may include hormones which can alsoaffect the secretion of insulin. Exogenous gluco-corticoids,24,25 glucagon,26,27 1 and growth hor-mone 28,29 exert reciprocal effects on the levels ofaminoacids and I.R.I. in the blood, and thus theiractions could not readily account for parallel abnor-malities of aminoacids and I.R.I. in obesity. Adrenalineis capable of lowering the levels of aminoacids andI.R.I. in the blood.30,31 The daily excretion of cate-cholamines by obese subjects in caloric balance is

normal,32 but there is indirect evidence of diminishedadrenal medullary responses to fasting in obese

subjects.33 Thus, reduction of adrenaline secretionin obese people in the postabsorptive state mightcontribute to elevation of aminoacids and I.R.I. inthe blood. These considerations illustrate the com-

plexity of the system in which metabolites andhormones interact in the regulation of insulinsecretion. More information is needed regardingdose-response relationships between insulin and itssubstrates, and in that light the demonstration ofabnormalities of specific aminoacids in obesity maylead to better understanding of metabolic andendocrine derangements in this condition.

21. Rabinowitz, D., Zierler, K. ibid. 1962, 41, 2173.22. Salans, L. B., Knittle, J. L., Hirsch, J. J. clin. Invest. 1968, 47, 153.23. Dupre, J., Curtis, J. D., Unger, R. H., Waddell, R. W., Beck, J. C.

ibid. 1969, 48, 745.24. Kretschmer, A., quoted by Noall, M. W., Riggs, T. R., Walker,

L. M., Christensen, H. N. Science, N.Y. 1957, 126, 1002.25. Perley, M., Kipnis, D. New Engl. J. Med. 1966, 274, 1236.26. Landau, R. L., Lugibihl, K. Metabolism, 1969, 18, 265.27. Samols, E., Marri, G., Tyler, J., Marks, V. Lancet, 1965, ii, 1257.28. Bartlett, P. D., Gaebler, O. H. J. biol. Chem. 1953, 196, 1.29. Luft, E., Cerasi, E. Lancet, 1964, ii, 124.30. Noall, M. W., Riggs, T. R., Walker, L. M., Christensen, H. N.

Science, N. Y. 1957, 126, 1002.31. Porte, D., Graber, A., Kuzuya, T., Williams, R. H. J. clin. Invest.

1965, 44, 1087.32. Pinter, E. J., Pattee, C. J. J. clin. Endocrin. 1968, 28, 106.33. Januszewicz, W., Sznajderman-Ciswicka, M., Wocial, B. ibid. 1967,

27, 130.

Joint ReplacementTHOUGH joint replacement was always the aim in

operating on joints ruined by disease or injury, it hasoften been necessary to make do with less-to adviseeither an arthrodesis, with stability but no mobility,or a pseudarthrosis, with mobility and reduced

stability. A pseudarthrosis is achieved by removingsufficient bone to produce a freely moving fibrousconnection to replace the joint (Keller’s operationfor hallux valgus is, of course, a pseudarthrosis, as isthe Girdlestone operation on the hip, both ofestablished value). Arthrodesis of the knee, ankle,and wrist are also operations which should holdtheir positions in the future, almost as securely as inthe past, because in these joints stability is thedominant need.

In arthroplasty the aim is to obtain stability withmobility. Success has not been as great as was hoped,but the introduction of total joint replacement has un-doubtedly changed the picture. Some encouragingresults, however, do not mean that arthroplasty ofmajor joints should be used in all cases; fusion of theknee or hip in a young person is still the best treat-ment because the daily demands are too great andthe period of use is too long for an arthroplasty togive continuing good results. It is generally agreedthat there must be some inherent restriction on thedemands on a major arthroplasty-such as is

imposed by the polyarthritis of patients withrheumatoid arthritis and by the age of those withosteoarthritis.

Total joint replacement could be either jointtransplantation or replacement with an inert pros-thesis. Among the interesting work in Russia, bothexperimental and clinical, on articular bone trans-plants, that of IMAMALIEV and his colleagues at theCentral Institute of Traumatology and Orthopxdicsin Moscow is particularly notable. They have hadsome success with transplantation of bone ends,including the articular cartilaginous surface, but theywere not so successful when the whole joint wastransplanted. The grafts were, of course, homograftstaken from cadavers.

Homograft arthroplasty, however, is still experi-mental, and clinically joint replacement means inertprostheses. It was in the hip that the early advanceswere made. The cup or mould prosthesis has beenwidely used since the late 1930s, by which timeSMITH PETERSEN of Boston had established the

operation; the cup arthroplasty still has its advocates,and in the past thirty years it has proved its ability tostand the test of time in some cases. The operationis designed to allow free movement of the boneson each side of the cup (the cup in the acetabu-lum and the femoral head within the cup) and theonly foreign material implanted in this operation is1. Imamaliev, A. S. in Recent Advances in Orthopædics; chap. VII.

London, 1969.

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the vitallium cup. Though absorption of the femoralneck and loss of movement or stability remain prob-lems and the failure-rate has never been small, cuparthroplasty has undoubtedly been successful in thehands of a number of surgeons. AUFRANC 2 has

improved the technique of this operation and claimsmore consistent results.The Judet acrylic head arthroplasty had a short

popularity, but the material proved totally inadequatefor the strains imposed on the hip-joint, and the aimof fixation of the acrylic prosthesis to the femoral neckby means of an exact fit proved quite unattainable. Afurther form of arthroplasty in which the femoralhead was replaced by a vitallium prosthesis becamevery popular in America, and was well established byAUSTIN MOORE.3 The degree of success largelydepended on the retained acetabulum which, if

spherical, conformed with the vitallium femoral headbut which, if misshapen, gave far less comfortableresults. With the Austin Moore prosthesis the fixationof the prosthetic stem to the femoral shaft relies onthe shape of the stem and on fenestra through whichbone is encouraged to grow. The material was

adequate for the demands imposed upon it, but oftenthe acetabulum would yield before the pressure of themetal. Sometimes, however, the sclerosis commonlypresent in osteoarthritis would avert this complication.The next step was the whole-hip arthroplasty,

developed independently by CHARNLEY 4 in Wright-ington and McKEE 5 in Norwich, and followed rapidlyby the work of RING s at St. George’s Hospital.The first two arthroplasties depend on the use ofacrylic cement, which takes an exact impression ofthe interior surface of the prepared bone and of theprosthesis, to form a perfect fit, but does not adhereto either. The acrylic cement sets in under tenminutes and is rock hard; it generates considerableheat when setting, but CHARNLEY has demonstratedliving bone next to the cement surface, with noreactive layer intervening. On engineering principles,CHARNLEY is averse to the use of similar metals for theacetabular and femoral-head elements; so he useshigh-density polyethylene for the acetabular elementand a stainless-steel femoral head; and he greatlyincreases the loading by reducing the diameter of thefemoral head to 22-25 mm. The acetabular elementwas formerly made in fluon, but this proved unable towithstand the loading. High-density polyethylenehas been in use since 1962 and it is proving adequate,provided that a built-in limit to demand exists in thepatient, either from age or from polyarthritis.CHARNLEY does not advise arthroplasty in osteo-

arthritis unless the patient is in the late sixties.McKEE’s femoral and acetabular elements are both2. Aufranc, O. E. in Campbell’s Operative Orthopædics; p. 1385.

St. Louis, 1956.3. Moore, A. T. J. Bone Jt Surg. 1957, 39A, 811.4. Charnley, J. Congr. Soc. int. Chir. Orthop. Traumat. 1967, x, p. 311.5. Mc Kee, G. K., Watson-Farrar, J. J. Bone Jt Surg. 1966, 48B,

245.6. Ring, P. A. ibid. 1968, 50B, 720.

of vitallium. The diameter of the femoral head in the

original pattern was 50-8 mm., but he has latelyintroduced an alternative prosthesis with a diameterof 44-5 mm. He is prepared to accept rather youngerpatients than CHARNLEY. Much more time is neededbefore the merits of the two arthroplasties can beassessed, though the intermediate results are verypromising.

In the third type of hip arthroplasty in use in thiscountry, RING s dispenses with cement and relies ona 3-inch threaded stem, passing up the thick boneposteriorly in the pelvis, which follows the weight-bearing line, reaching almost to the sacroiliac joint.This he finds gives adequate fixation to the acetabularelement with its cone seating, while the femoralelement relies on its shape and fenestration forfixation in the femur, in the same way as with theAustin Moore femoral replacement. The Ringarthroplasty will certainly have an appeal if its

performance equals that of the Charnley and McKeearthroplasty, since, by avoiding acrylic cement, itlimits the amount of foreign material introduced andmakes the prosthesis acceptable in countries whichhave not sanctioned the use of acrylic cement (in theUnited States its use is permitted only in certainspecial centres).These three whole-hip arthroplasties have given

some excellent results. Function often closelyimitates the normal, and even patients who have hadbilateral operations can play golf and tennis. The

very excellence of the results creates problems sincethe demands made by the patient become muchgreater than expected. Understandably, the youngerpatient does not now relish the suggestion of anarthrodesis and the demand for arthroplasty grows.In the matter of cost, the Charnley arthroplasty withthe cement costs about E18, the McKee arthroplastycosts about E70, and the Ring E90. For each

operation, the period in hospital should not exceedfour weeks. Elderly people stand this type of

operation very well, and it can be offered to patientsinto their eighties. The greatest risk is undoubtedlysepsis, and the presence of foreign material createsadditional problems. To counter sepsis CHARNLEY 7has his own special operating-room within the

operating-theatre. Here the surgeon and his assistantsand the patient below the level of his neck occupya glass-walled area supplied with specially filtered airdriven in from the top and escaping through ventsnear the floor. The surgeon and his assistants exhale

through tubes attached to their face-masks, so that thewound is free from all air contamination. Sepsis canbe a disaster, calling for the removal of all foreignmaterial. In such cases a Girdlestone type of pseud-arthrosis may be formed, once the infection has beencontrolled. In other cases a small sinus can developlater; but it can be well tolerated without deteriora-tion. It is surprising how late infection can strike:

7. Charnley, J. ibid. p. 822.

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infection from the original operation may not declareitself for up to two years; or a subsequent bacteraemiamay lodge infection in a hip where some failure offixation has produced an area of low resistance. In180 hip operations since 1964, RING had only 1 caseof sepsis and 1 of mechanical failure-excellent

figures for an intermediate report. PARSONS 8 analysedthe results of whole-hip arthroplasty operations atthe Royal National Orthopaedic Hospital: in 200

hips, sepsis developed in 6, and in 5 of these theprostheses and cement had to be removed, whilein the 6th the sinus and stiff hip were tolerated.In 11% there was some loosening of the prostheticelements, often calling for a second operation, butwith the newer prosthesis this complication hasbecome much rarer.

In the knee-joint a stable result from any operationis so important that fusion has usually been advocated,even in polyarthritis. McINTOSH,9 of Toronto, hasdesigned a hemi-arthroplasty, in which a vitalliumdisc is introduced on one or both sides of the knee-

joint after a small disc of the tibial plateau has beenexcised, thus improving the surfacing of the joint andrestoring stability by the slightly deeper vitalliumdisc used in the replacement. A range of heights ofthese discs enables ligaments to be tightened. Twovaluable total knee arthroplasties have been designedby WALDIUS 10 of Sweden, and SHIERS 11 in this

country. At their introduction neither of thesemethods made use of acrylic cement. The broad sur-face of contact with the cancellous bone of the femurand the tibia in the Waldius arthroplasty has givenvery satisfactory results in rheumatoid arthritis.12SHIERS has advocated the use of cement in the fixationof the two elements in his arthroplasty; and there areeven those who advocate cement for fixation in theWaldius operation. Many believe that this change intechnique carries serious dangers. The knee arthro-plasty is almost subcutaneous in places, and the riskof infection is greater; in the absence of cement, the

prosthesis can be readily removed and arthrodesisaccomplished without difficult. Not so when thecancellous bone has been largely removed and

replaced by cement. Knee arthroplasties really haveno place in a vigorous osteoarthritic person, but theyare a great help in patients with rheumatoid arthritis,for whom the ability to flex the knee is vital in

retaining independence.In the arm, arthroplasty has not developed very far.

The humeral head may be replaced after removal ofa tumour, but usually there is great loss in control ofthe shoulder-joint. The replacement of a damagedradial head or a semilunar bone by acrylic implantsdoes not seem to improve function more than simpleremoval of the deformed or ischaemic bone. Arthro-

8. Parsons, D. W. ibid. 1969, 51B, 564.9. McIntosh, D. L. ibid. 1966, 48B, 179.

10. Waldius, B. ibid. 1968, 50B, 221.11. Shiers, L. G. P. ibid. 1965, 47B, 586.12. Blundell Jones, G. ibid. 1968, 50B, 505.

plasty of the fingers is of considerable value and, hereagain, it is in rheumatoid arthritis that most benefithas been secured. The small hinge joints introducedby FLATT 13 were widely used, but SWANSON 14 haslately provided ’ Silastic ’ prostheses, for both meta-carpophalangeal and interphalangeal joints. These

prostheses gain fixation to the bones by intra-

medullary extensions and move only in one plane.They seem to offer great promise but it is too earlyfor more than a tentative assessment. In the meta-

carpophalangeal joints many surgeons still favour thepseudarthroses provided by excision of the heads ofthe metacarpals.

Joint replacement has undoubtedly come to stay;and it is already thoroughly established in the hip-joint. The principle is well accepted in operations onthe knee, although in the more restricted area ofcrippling rheumatoid arthritis. Operation for replace-ment of major joints is still limited to patients whowill make modest demands on the joint, leavingarthrodesis to provide the robust function demandedby the young and vigorous.

RABIES

ANOTHER inquiry into the disturbing rabies situationin Britain is now in hand after a dog died of the diseasein Newmarket last week. The three-year-old bitchhad been brought from Pakistan last May and wasreleased from quarantine at the end of November

(the dog which died in Camberley in October hadbeen only ten days out of quarantine). This new

death, as long as three months after release from sixmonths’ quarantine, again raises questions about theefficiency of this country’s defences against rabies.Events in recent months suggest either that theincubation period can be longer than the prescribedtime of quarantine (increased to eight months afterthe Camberley incident) or that the possibility ofinfection by indirect contact 15 during quarantine hasbeen underestimated. Certainly the results of the

post-Camberley inquiry did not exclude such a meansof spread. Since these uncertainties persist and sincethe consequences of rabies escaping into wild carrierswould be so grave, pressure for the total exclusion ofall potentially infected animal immigrants will

certainly now increase.

STRESS, MULTIPLE SCLEROSIS, ANDCORTICOSTEROIDS

THE plaques of multiple sclerosis are often foundaround the walls of the third ventricle, suggestingthat some abnormality of hypothalamo-hypophysialfunction might be present in these patients. Thereare also pointers to indicate that corticosteroids playa part in the relapses and remissions of the disease.Relapses may be precipitated by various stresses,

13. Flatt, A. E. ibid. 1961, 43A, 753.14. Swanson, A. B. Hond. 1969, 1, 38.15. Lancet, 1969, ii, 1313.