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Page 1: REGENERATION AFTER NERVE INJURIES

762 REGENERATION AFTER NERVE INJURIES

MORE ABOUT INFLUENZA VACCINESNEWS has come in from time to time during the last

few years of trials of influenza virus vaccines on man.The general conclusion from the tests has been thatsome protection can be achieved, but this has not yetbeen sufficiently encouraging to justify the use -ofvaccines on a large scale. Now things are looking up.While reports published in 1941 held out hopes of, atbest, halving the incidence by inoculation, recenttrials offer prospects of a three- or four-fold reduction.An influenza A epidemic occurred in the USA duringthe last quarter of 1943, at about the time of the out-break over - here. In nine communities under six

groups of observers 2 vaccination studies had beenplanned, and 6263 persons were injected subcutane-ously with inactivated virus (A and B), 6211 othersserving as uninoculated controls. Several previoustrials of vaccine, both here and in the USA, havemiscarried because influenza has failed to appearwithin a reasonable time. But on this occasion theluck was in : the wave of influenza broke at the

optimum time, in most groups 2 or 3 weeks after thevaccinations. The incidence of clinical influenza inthe vaccinated people of the whole series was 2-22%,in the controls 7’11%, a ratio of 1 to 3,2. Only onegroup of the nine failed to show a substantial differencebetween the treated and untreated groups ; this was inCalifornia, where, among other factors, there was arather longer interval between vaccination and theonset of the outbreak. Exclusion of this group would

bring the ratio to 1 : 3’6 in favour of the vaccinees.It is of great practical importance to determine the

reason for this good result. One factor may well havebeen the great stroke of luck that the epidemic fol-lowed the vaccinations so promptly. A rather briefduration of the increased immunity after vaccinationis suggested by trials 3 carried out in America in1942-43 when groups of volunteers vaccinated againstinfluenza A were subsequently exposed to activevirus by inhalation ; the results were assessed by thedegree of febrile response. Against virus A, vaccina-Hon 2 weeks before exposure reduced the incidence offever (over 100° F.) from 50% to 14-3%. Of a groupvaccinated 4t months before exposure, 32% hadfever-no significant reduction from the control figure.Against virus B, however, vaccination reduced theincidence of fever from 41 % to about 10% irrespectiveof whether the inoculations had been made 4t monthsor 2 weeks previously. There have been earlier

suggestions that virus B is a better antigen than A.A second possible factor may have been the nature ofthe vaccine used. A formalin-inactivated vaccinemade from the allantoic fluid of infected chick-

embryos was used, two strains of virus A and one of Bbeing represented. The virus had been concentratedten-fold by adsorption on, and subsequent elutionfrom; embryonic chicken red-cells by the method ofFRANcis and SALK.4 We badly need to know whetherthe use of more concentrated vaccine was indeed the

determining factor, for a ten-times concentratedvaccine means that only a tenth as much vaccinecan be made from a given number of eggs.1. Horsfall, F. L. jun., Lennette, E. H., Rickard, E. R. and Hirst,

G. K. Publ. Hlth Rep. Wash. 1941, 56, 1863.2. US Commission on Influenza, J. Amer. med. Ass. 1944, 124, 982.3. Francis, T. jun., Salk, J. E., Pearson, H. E. and Brown, P. N.

Proc. Soc. exp. Biol., N.Y. 1944 55, 104. Salk, J. E., Pearson,H. E., Brown, P. N. and Francis, T. jun. Ibid, p. 106.

4. Francis, T. jun. and Salk, J. E. Science, 1942, 96, 499.

Should we, at this moment, be aiming to have avail-able influenza vaccines on a large scale ? 1 We have

just been through an influenza A outbreak,fortunatelya mild one. According to the rules, we should not beafflicted by virus A next winter ; but can we trust thevirus to obey the rules ? 1 Ought we to be vaccinatingagainst a possible influenza B epidemic ? 1 It is truethat no really serious B outbreak is known to haveoccurred over here, but there was a big one in theUSA in 1936. The evidence indicates that the im-

munity following vaccination, at least against A, isfleeting. Widespread use of precious vaccine thisautumn on the off-chance of an epidemic seems

therefpre inadvisable. Much more reasonable wouldbe the.provision of vaccine on a large scale, ready to beused immediately the red light showed. Such a

policy would imply that epidemiological and labora-tory workers must collaborate to watch for an out-break and identify the causative agent promptly.Finally, is there any likelihood that vaccine would,if we wanted it, be available ? 1 One could not justifyits manufacture over here at the expense of thepublic’s meagre quota of shell-eggs. Eggs exist, webelieve, across the seas, but is any country likely to beable to make more vaccine than it can easily useitself ? 1 It is clear that many difficult problems arise ;" of that," as the Grand Inquisitor remarked,

’’ thereis no possible doubt whatever."

REGENERATION AFTER NERVE INJURIESTHE alignment of surgical treatment with patho-

logical histology is nowhere more important than ininjuries of the peripheral nerves. In the war of1914-18 a good knowledge was acquired of the

changes that follow complete division of nerves,and both clinical and experimental work in thisfield have been considerably extended in the past fewyears. Less is known both of those " lesions in

continuity," in which wallerian degeneration occursalthough the injury does not entail anatomicalseverance of the nerve, and the condition known as"transient block," in which recovery is rapid andcomplete and is unaccompanied by wallerian degenera-tion of the peripheral portion of the nerve. In a

study by SEDDON, based on 650 cases, these threetypes of disturbance are analysed and defined fromthe practical standpoint of the surgeon who has totreat them.To the first group, in which there is complete

severance of the nervous elements, the name neuro-’tmesis is given. This injury most often accompaniesopen wounds. The subsequent phases of degenera-tion and regeneration have been worked out withconsiderable precision by J. Z. YourrG and his Oxfordcollaborators. Spontaneous regeneration is rare andalways imperfect ; hence operative interventionis necessary. The term axonotmesis is applied to thesecond group in which the nerve lesion is in continuity.Blunt injury is the commonest cause. The nerve-fibres are sufficiently damaged to entail wallerian

degeneration of the peripheral portion of the nerve,but the supporting structures are intact. Recoveryhere is spontaneous, satisfactory and fairly rapid ;it may be presumed that the regenerating fibres growalong the old paths and reach their appropriate1. Seddon, H. J. Brain, 1944, 66, 238.2. The names adopted for the three types were suggested by Prof.

Henry Cohen.

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destinations. This recovery is essentially superior.to that obtained in cases of neurotmesis after nerve-suture, probably because of the grave confusion ofthe intraneural topography in the latter. As SEDDON

puts it, " one result of this confusion is an all-rounddecrease in the population of functioning fibres in theperipheral stump." The integrity of the Schwann

,

tube is evidently of fundamental importance in theprocess of regeneration. In view of the differencesin prognosis and treatment it is thus important todistinguish clinically between neurotmesis and axono-tmesis. The surgeon will be influenced first by the

. nature of the injury. Thus with a closed fracturecomplicated by paralysis the chances are about20 to 1 infavour of axonotmesis, in SEDDON’s estimate.On the other hand a gunshot wound causing shatter-ing of a bone may well divide the nerve at the sametime. Secondly, one can estimate the time at whichsigns of spontaneous regeneration would be expected,since motor fibres grow about 1-5 mm. a day. Adding40-50 days for the latent period before growth beginsit is thus possible to calculate the approximate timewhen function should return to the first muscle

supplied below the site of the lesion, and delay willthen point towards neurotmesis as the diagnosis.But where this muscle is a considerable distancefrom the lesion the calculated time for regenerationmay be unduly long to wait before carrying out suture,if it is eventually required. SEDDON therefore laysdown the rule that " it is desirable to carry out earlyexploration in almost all high lesions that have

produced complete paralysis." If the nerve, when

exposed, shows clear evidence of intraneural fibrosishe recommends resection and suture. However,grades of intraneural damage are sometimes encoun-tered without loss of continuity of the nerve-sheath,making the clinical distinction between axonotmesisand neurotmesis no easy matter.In the third form of nerve injury, neurapraxia,

there is a transient block producing a paralysis whichis of shorter duration than would be expected if

complete wallerian degeneration had taken place.Motor paralysis in these cases is almost invariablygreater than sensory, and is usually complete ; thereis little or no wasting of the muscles and their electricalexcitability is unchanged. There was evidence insome of SEDDON’S cases of a mixture of neurapraxiaand axonotmesis, and in these there was some muscle-wasting. The -pathological basis of neurapraxia hasbeen a puzzle for many decades. The experimentsof DENNY-BROWN and BRENNER,3 in which paralysis

. was induced in cats either by direct pressure on thesciatic nerve or by the application of a tourniquet,are of great interest in this connexion. Using directpressure they found great variability in the rate andextent of impairment of conduction. This appearedto be due to difficulty in controlling the blood-vessels within the nerve, since perfusion with indianink at a pressure just below the estimated systolicblood-pressure showed that a large longitudinalvessel running through the compressed area was filledin spite of the greater external pressure applied atthat site. Thus variable degrees of ischaemia mayhere be responsible for the impaired conduction.

, No evidence of structural damage was found on3. Denny-Brown, D. and Brenner, C. Arch Neurol. Psychiat. 1944,

51, 1.

histological examination in this series of experiments.Application of a narrow-cuff to the thigh at a pressureof 50 cm. of mercury for 2 hours and 6 minutes pro-duced varying degrees of paralysis in cats. Where

impairment of conduction lasted 1 to 19 days orlonger, without loss of gross sensation or excitabilitybelow the lesion, there were focal histological changesat the site of the lesion-early vacuolation andswelling of the axis-cylinders, vacuolation of the

myelin sheaths, and later, disappearance of myelinbeginning at the nodes of Ranvier. The axis-

cylinders lost their affinity for silver at the site of thelesion though they could be stained with iron haema-toxylin. The Schwann cells remained intact thoughthere was considerable infiltration of the sheaths withmacrophages. In the process of recovery the axis-

cylinders acquired a fresh, thin myelin sheath, butmore than two months was necessary for completerestitution. Fibres of any calibre might be affectedby these changes ; thus the prevailing view thatthose of large calibre are selected in an ischaemiclesion of this kind is not supported. The reason whymotor disturbance predominates in neurapraxia istherefore still to seek.

RURAL HOUSINGTHE third report to the Ministry of Health (HMSO.

Pp. 67) of Sir Arthur Hobhouse’s committee is goodvalue at a shilling. The committee was representative :among others, a doctor (the late Sir Francis Fremantle),six public women, Sir Seymour Williams (of the RDC’sAssociation), the clerk of a go-ahead district counciland the chairman of a county council, a parson, twomembers of the farm workers’ organisation, Sir FelixPole (who used to look after railway hotels and is acountryman), a peer, an MP, and the editor of the

Countryman, who is a county councillor and a JP.The most important recommendations are that housingshall remain the business of the district councils, butthat the county councils shall bear in mind that theirduty, under the Housing Act, 1936, is to have " aconstant regard " to the condition of housing in theirarea, and -that the housing experience of each countyshall be pooled in a joint county and rural committee.Further a national survey of housing conditions shouldbe made and kept up to date. It is urged that thereshall be on the staff of all county medical officers asanitary officer to advise on rural housing, that districtmedical officers, in their yearly reports, shall give " afull and informative " account of housing conditions,and that a larger number of competent- sanitary in-

spectors shall be available. The committee is clearthat district councils should have architects-architectswith experience of rural conditions-that there oughtto be more women on the councils, and that some of thesmaller councils should be amalgamated. As might beexpected, a maximum extension of water and electricityservices is pressed for, and the fact is faced that, in manydistricts, rating assessments should be higher in orderthat money may be - available for essential services.

Finally, the Ministry itself is counselled to be a bit morealert and up to date. When to this Hobhouse Committeereport is added the report of Lord Dudley’s committee,the country will be left in no doubt as to what so muchwants doing in rural housing and how it should be setabout.

MOH SCHOOL MEDICAL GROUP.—Mr. R. A. Butler, presi-dent of the Board of Education, will address this group atthe London School of Hygiene on Friday, July 21, at 3 PM,on the place of the school medical service in the educationalservices of the future.

RURAL HOUSING


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