1152

there is still scope in this direction-for example, in thedevelopment of methods for measuring micro or submicroamounts of drug in body-fluids, so that its disposition andfate in animals and man can be more accurately followed.14

AN INSTITUTE OF THERAPEUTICS

In 1959 the Hinchliffe Committee said: " The presentarrangements for the organisation and interpretation ofsuch (clinical) trials and for the publication of results areinadequate." 15 Five years later the situation is worse andis continuing to deteriorate. There are several ways inwhich it might be improved; but every cause needs achampion, and it is difficult to see how any of the changescould come about of their own accord. A positive effort isneeded, but at present it is no-one’s job to make it.

For some years one of us has canvassed the idea of anInstitute of Therapeutics. Several of the functions origin-ally proposed for it have since been taken over by othernewly created organisations, but there still seems to be aneed for a body to support therapeutics as a scientific

discipline. Such an institute could:Foster undergraduate . and postgraduate training in

therapeutics and clinical investigation.Support studies on methodology, including operational

research.Advise individuals, institutions, and if necessary the

Government, on training, on the best method of usingavailable facilities, and on future trends.

Raise money and allocate grants-e.g., for fellowships.Although at the moment it seems to’ lack a lead, the

pharmaceutical industry has offered financial help to

improve trial facilities,Io and there is no reason why moneyshould not be raised elsewhere.

Others facing the same problems are thinking alongsimilar lines. In Canada a Foundation has been created" to stimulate the improvement of drug evaluation

procedures". It will be concerned primarily with grantingfunds for training and research.16 17 Still more recentlythe United States National Academy of Sciences hasappointed a drug research board to " foster the orderlyprogress of therapeutic research in the development andevaluation of drugs". The board will act in an advisorycapacity and will attempt to reconcile the needs of

investigators, industry, and the Government.18CONCLUSIONS

No-one can feel complacent about the present qualityor scale of clinical trials. They are an increasingly seriousbottleneck in the development and effective use of drugs,but no real attempt has yet been made to tackle the

problem.Better use could be made of resources already available.

The following questions deserve study:How to match facilities and case material.How to overcome practical difficulties.The value and limitations of specialist associations and

hospital research committees.Methods of providing physical and financial support.Why so few doctors undertake drug research; what

motivates those who do.

We probably need additional resources: more academicdepartments, a fellowship scheme, and an Institute ofTherapeutics.To allocate priorities in terms of men, materials, and

money, a programme of operational research should be14. Brodie, B. B. in Absorption and Distribution of Drugs (edited by T. B.

Binns). Edinburgh, 1964.15. Ministry of Health. Cost of Prescribing. H.M. Stationery Office, 1959.16. Canad. med. Ass. J. 1963, 88, 1299.17. Murphy, C. W. ibid. 1963, 89, 1298.18. Med. Trib. 1963, 4, 6.

drawn up. In particular, those who actually do the workshould be asked what their problems are.To organise this research with sufficient authority, and

to ensure that the results and recommendations carry

enough weight to be put into effect, we recommend that asmall committee of the highest standing should be created,

SUCCESSFUL REATTACHMENT

OF A COMPLETELY SEVERED FOREARM

A COMMENTARY

J. S. HORNM.B. Lond., F.R.C.S.

OF THE INSTITUTE OF ORTHOPÆDICS AND TRAUMATOLOGY,CHI SHUI TAN HOSPITAL, PEKING

SALVAGE of incomplete traumatic amputations has beenreported,occasionally 1 2 but, so far as I know, no cases inwhich a completely amputated extremity was reattached,survived in its entirety, and regained good function. Afull account of the following case appeared in the ChineseMedical Journal.3

CASE-REPORT

On Jan. 2, 1963, a male factory worker, aged 27, caught hisright hand in a machine and sustained a clean traumaticamputation just proximal to the wrist (fig. 1). He was immedi-ately sent to the nearest hospital-the Shanghai Sixth Municipal

Fig. I-Stump and amputated hand on arrival of patient at hospital.

Hospital. This is the usual type of 400-bed general hospitalto be found in most of the large cities of China, possessing noout-of-the-ordinary equipment or facilities. The amputatedextremity was wrapped up in clean cloth and was also sent to thehospital.On arrival, the patient’s blood-pressure was 130/80 mm. Hg.

The patient was not in a state of shock, and, although notourniquet had been used, there was no active bleeding fromthe stump. Dr. Ch’en Chung-wei and Dr. Ch’ien Yun-chingoperated on him and were responsible for his subsequenttreatment.

OperationTreatment of the amputated extremity.-The amputated

extremity was thoroughly washed with sterile soap and salinesolution, and the exposed soft tissues were carefully exciseduntil only healthy-looking tissue remained. A slice of bone0-5 cm. thick was sawn off from the severed ends of the radiusand ulna. Large quantities of 10% heparin in physiologicalsaline were instilled into the cut end of the radial artery, and theblood-vessels of the hand were irrigated until the fluid returningfrom the severed veins was clear.4-7

Treatment of the proximal stump.-Under brachial-plexus1. Salesses, Moussu, Aupecle (Rapport de M. R. Soupault) Mém. Acad.

Chir. 1962, 88, 32.2. Kleinert, H. E., Kasdan, M. L., Romero, J. L. J. Bone Jt Surg. 1963,

45A, 788.3. Ch’en, C. W., Ch’ien, Y. C., Pao, Y. S. Chin. med. J. 1963, 82, 632.4. Breidenbach, L., Lord, J. W. Amer. J. Surg. 1948, 76, 578.5. Ferguson, I. A., Sr., Byrd, W. M., McAfee, D. K. Ann. Surg. 1961,

153, 980.6. Seidenberg, B., Hurwitt, E. S., Carton, C. A. Surg. Gynec. Obstet. 1958,

106, 743.7. Shaw, R. S. J. Bone Jt Surg. 1959, 41A, 665.

1153

block supplemented towards the end of the operation by etheranesthesia, the proximal stump was thoroughly cleansed, andragged tissue was excised. No tourniquet was used. Slices ofbone 0.5 cm. thick were cut off the exposed ends of the radiusand ulna. The ends of the radial and ulnar arteries were in

spasm: the intima had retracted and the vessels containedblood-clot. Both arteries were dissected proximally for 1-5 cm.and their traumatised ends were trimmed up to completelynormal-looking artery. A spurt of blood was allowed to gushfrom each artery to flush out small clot fragments, and bleedingwas then controlled by atraumatic clamps applied directly toeach vessel.

Repair.-The first step was to provide rigid internal fixationfor the severed radius. This was accomnlished bv usins a

stainless-steelplatebentto fit the lower frag-ment and held by twoscrews in each frag-ment. Then the peri-osteum,the interosseousmembrane, and theflexor pollicis longustendon were suturedwith interrupted 00silk. The distal stumpsof the flexor digitorumprofundus were at-

tached to the proximalends of the flexor digi-torum sublimis tendons

by Bunnell’s technique.In this way a good bedwas provided for thevascular anastomosis,and the possibility ofstrain on the anastomo-

sis, which would haveexisted if the tendon

repair had been doneafter the anastomosis,was obviated. Next theradial and ulnar

arteries were anastomosed using short lengths of 2-5 mm.internal diameter polyethylene tubes as cuffs (fig. 2). Thearterial anastomosis was completed four hours after the

injury, after which the hand immediately became flushedand retrograde bleeding occurred from the severed veins.Then the cephalic and ulnar veins were anastomosed withinterrupted sutures of 000000 silk. Next, the severed endsof the median and ulnar nerves and the dorsal branch ofthe ulnar nerve were excised back to healthy tissue and

accurately approximated by interrupted silk sutures throughthe nerve sheaths. Finally, the superficial wrist flexors-the flexor carpi ulnaris and radialis-and all the extensors ofthe wrist, fingers, and thumb were individually sutured with00 silk according to Bunnell’s technique. The skin wound wasdosed after rearranging the skin so that the suture line wasZ-shaped, to avoid subsequent constriction by contracture of an

Fig. 2—Method of anastomosis of ulnarand radial arteries using polyethylenecuffs.

Fig. 3-Hand immediately after operation. Congestion of veins ondorsum of hand.

annular scar (fig. 3). The limb was supported on a plaster-of-paris splint. The entire operation took about seven hours.

Early Postoperative CourseHeparin was given postoperatively for three days by intra-

venous drip in sufficient dosage to maintain the clotting-timeat about twenty minutes. Papaverine was given by mouth forten days with the object of preventing vascular spasm.a-10The hand and forearm were maintained at room temperature

(about 25°C), and the patient was given prophylactic antibiotics.On the first postoperative day, the fingers were 1-2°C warmerthan those of the uninjured side. On the second day, the handbegan to swell rapidly, and the fingers became cool. Conse-

quently, the hand was decompressed three days after injury bymeans of longitudinal incisions on the dorsum of the hand andalong the midlateral lines of the fingers. During this operationthe pressure in the veins on the dorsum of the hand wasmeasured and found to be 40 cm. of water. Hypertonic salinecompresses were repeatedly applied to the incised woundsunder strictly aseptic conditions, and the swelling graduallysubsided. The sutured wound healed by first intention, andthe sutures were removed after two weeks. The decompressionincisions healed by second intention within three weeks. Afterthe hand had completely healed, a course of active exercisesand physiotherapy was begun and the patient progressedrapidly.Second OperationOn April 6, 1963, the patient was operated on again. There

were two reasons for this. One was that radiography showedthat neither the radius nor the ulna showed signs of bony union.A false joint between the fragments of the ulna had beenexpected, because the line of section was close to its lower endand no attempt had been made to immobilise it or to maintainbony contact, and a false joint in the ulna would in any eventhave been advantageous in increasing the range of pronationand supination. The other indication for operation was thatarteriography had shown that, although the radial and ulnararteries were patent, there was significant stenosis of the ulnarartery.At operation the steel plate and screws were removed, and

Phemister-type bone grafting with autogenous iliac bone chipswas carried out. The plastic cuff around the ulnar-arteryanastomosis was removed by slitting it with scissors and divid-ing the encircling silk ligature (fig. 2). The opportunity wastaken to inspect the suture lines in the nerves and tendons, andall were found to be satisfactory. A few adhesions were divided,and a small amount of scar tissue which had formed around thesites of nerve suture was excised.

Subsequent ProgressAfter the bone-grafting operation, the radius quickly united

by bone. A pseudo-arthrosis developed in the ulna.The first signs of nerve recovery were observed at two months

when sensation began to return in the palm of the hand.Electromyography at three months showed that the fibrillationcharacteristic of denervation were disappearing, and thatabnormally shaped polyphasic action potentials appeared inresponse to attempted voluntary contraction of the thenarmuscles. Shortly afterwards a flicker of voluntary contractioncould be detected in the thenar muscles, and thereafter both thepower and range of movement improved rapidly. Electro-

myography at seven months showed a nearly normal conditionwith efficiency of impulse transmission about 90% of that on theuninjured side.

Follow-upI examined the patient eight months after injury. The

temperature and colour of the skin were about the same on thetwo sides. Both radial and ulnar arteries could be felt pulsating.Sweating and sensation had returned throughout the hand.Light touch was appreciated on the pulps of all the fingers, buttwo-point discrimination and stereognosis were defective.Temperature discrimination was within 1-2°C according to

8. Urschel, H. C., Roth, E. J. Ann. Surg. 1961, 153, 611.9. Harold, F. B. J. Bone Jt Surg. 1962, 43A, 193.10. Murray, G. Arch. Surg. 1940, 40, 307.

1154

which finger was testedand the actual range of

temperatures used.All the intrinsic

muscles of the handcould be made to con-tract voluntarily, andmuscle wasting was re-markably slight. The

range of passive move-ment of the fingers wasnormal; but active flexionwas slightly limited, andactive extension was sig-nificantly limited. Mostfingers could be flexed towithin 2 cm. of the palmand a satisfactory fistcould be made.

Wrist movements were limited both actively and passively,only 20° of active extension of the wrist being possible. Thiswas partly due to joint changes resulting from the proximity ofthe traumatic amputation and partly because the extensor

tendons had united with lengthening. The patient could

pronate through 60° and supinate through 80°. The shoulderand elbow were normal.The extent to which the hand had again become part of the

patient was quite remarkable.He used the hand normallyand naturally in gesticulating.He could knit at a fair speed,and he used the reattached

right hand in preference to

the left one for writing. Beforehis injury he had been re-garded by his workmates as

a very promising ping-pongplayer. Now he had resumedplaying ping-pong and hishand was strong enough toenable him to use a hammerand to lift moderately heavydumbbells. His good tactilesensibility, normal sweatingand skin texture, and amplerange of thumb movementsenabled him to hold a glass ofwater with complete assur-

ance (figs. 4 and 5). There isno doubt that function will

continue to improve, but already it is as good as one wouldexpect to follow a total repair of nerves and tendons in frontof the wrist.

DISCUSSION

The operation was performed unhurriedly, with carefultechnique. The cut was clean, and very little tissue hadbeen devitalised, and there was relatively little delaybetween the injury and the restoration of circulation."The use of plastic cuffs in anastomosing the radial and

ulnar arteries simplified the procedure and probablyhelped to maintain patency of the vessels in the all-

important early postoperative period. At a later phase,they may have resulted in slight stenosis of the vessels but,if so, this produced no clinical ill effects.The decision to use internal fixation on the radius was

undoubtedly correct. If rigidity had not been restored,the anastomosed vessels would have been subjected totwisting, bending, and traction strains which might havehad disastrous results.The advisability of primary nerve suture will be ques-

tioned by many, but in this case it paid handsome divi-

Fig. 4-Hand grip eight months afteroperation.

Fig. 5-Reattached hand usedin play.

11. Hardy, E. G., Tibb, D. J. Brit. med. J. 1960, i, 1001.

dends; for recovery of function both in the ulnar andmedian nerves was unusually complete. In my opinionthe decision was correct because (a) the extent of theintraneural scarring was, from the nature of the injury,not likely to be great; (b) shortening of the bones permitteda radical excision and accurate approximation of the nerveends; (c) the lesion was low and the earliest signs ofrecovery could be expected within a few weeks. If signs ofrecovery had not appeared then, it would not have beentoo late to re-explore and resuture with expectation of agood result.

Since this case Dr. Chen has successfully reattachedtwo more completely amputated limbs. In dealing withthese, he paid particular attention to anastomosing mostof the venous channels, and as a consequence the limb didnot become oedematous.

MUST MACKINTOSH SHEETS BE USED TOCOVER PATIENTS AT OPERATIONS?

J. A. C. WEATHERALLM.B., B.Sc. Edin.

H. K. ASHWORTHM.B. Manc., F.F.A. R.C.S.

H. J. CRAWFORDM.B., B.Sc. Lond., M.R.C.P.

B. MURPHYM.B. Lond., D.Obst.

H. I. WINNERM.A., M.D. Cantab., F.C.Path.

From the Departments of Bacteriology and Anœsthetics,Charing Cross and Fulham Hospitals, London.

IN many operating-theatres it is still customary to coverthe patients with mackintosh sheets under sterile towelsduring operations. The reason usually given is thatmackintoshes can prevent bacteria from the patient’s skinreaching the operation site. Anarsthetists find that the useof mackintoshes, especially during long operations, makesit extremely difficult to control the patient’s body tempera-ture, and in some cases leads to hyperthermia. Conse-

quently we undertook some experiments to determinewhether in the absence of mackintoshes contamination ofthe operation site was an appreciable risk, and whetherthe risk was reduced by the use of mackintoshes.

METHODS

The experiments were conducted in the main theatres at

Charing Cross and Fulham Hospitals. In the first series,alternate operations were performed either with sterile mackin-toshes or with nothing between the skin of the patient and theoperation towel. The surface of the towel was sampled forbacteria by placing a standard sterile beaker, underside upper-most, under the towel, and inverting a sterile petri dish contain-ing blood-agar over the beaker so that it made contact with thetowel. The petri dish rested in position for about 15 seconds.One sample was taken from each operation and samples weretaken either 1 hour, 45 minutes, or 30 minutes after the start ofthe operation. The site sampled was usually over the pubiswhere instruments had been laid during the operation. Each

agar plate was incubated for 24 hours and the numbersof colonies on the surface were counted. The results are

summarised in the accompanying table.In a second series of experiments the surface of towels was

also sampled by direct contact with an agar surface, but themethod described by Lawrie and Jones (1952) was used. 8 in.of a sterile 2 in. bandage was embedded in a molten blood-agarplate. When cold, a disc of blood-agar gel could be lifted bythe bandage ends from the petri dish. The under surface ofthe disc was laid on the surface of the operation towel. Contactbetween the disc and the towel was maintained for 30 seconds.Where contact had been made the pattern of the towel couldbe seen on the surface of the disc. The disc was then turnedover, returned to the petri dish, and incubated for 24 hours.The number of colonies in four separate 1 sq. cm. areas wascounted. If no towel pattern was seen on a sampled area, no