493

reported an inquiry into the analgesic action of a seriesof compounds in which the N-Triethyl group of pethidineis replaced by a tertiary amino-alkyl group. Experi-mentally one of this series, morpholinoethylnorpethidine,is somewhere between three and seven times more potentthan the parent substance, yet without equivalent increasein toxicity. This analgesic seems well worth furtherinvestigation, but experimental findings are not alwayssubstantiated in clinical practice. In 1949 a piperidylanalogue of iso-amidone was found under experimentalconditions in both animals and man to be less depressantto respiration than morphine, pethidine, and amidone.4 5Clinical trial as an adjunct to nitrous-oxide anaesthesia,however, now suggests that it is not a satisfactorysubstitute for pethidine because of the severe respiratorydepression that it may cause ; and there is also somedoubt about the adequacy of analgesia. 6

4. Ofner, P., Thorp, R. H., Walton, E. Nature, Lond. 1949,163, 479.

5. Prescott, F., Ransom, S. G., Thorp, R. H., Wilson, A. Lancet,1949, i, 340.

6. Masson, A. H. B. Anœsthesia, 1956, 11, 59.7. Barr, M., Sachs, A. Army Pathology Advisory Committee

Report on the Investigation into the Prevention of Tetanus inthe British Army. 1955. w.o. code no. 11262.

8. Looney, J. M., Edsall, G., Ipsen, J., Chasm, W. H. New Engl. J.Med. 1956, 254, 6.

PROTECTION AGAINST TETANUS

INDEPENDENCE Day celebrations in the United Statesused to be responsible for many deaths from tetanus ;but the use of tetanus antitoxin in the treatment of theinjuries reduced the number of deaths from 100 per 1000injuries on Independence Day, 1903, to 3 deaths per 1000in 1913. In the early months of the 1914-18 war notenough tetanus antitoxin was available, largely becausethe incidence of tetanus had been negligible on SouthAfrican soil during the Boer war. The incidence oftetanus in 1914 was about 8 cases per 1000 wounded-a similar figure to that recorded during the Franco-Prussian war of 1870. But ample supplies of tetanusantitoxin were soon produced, and the incidence fell to1 per 1000 wounded. Yet, despite the way in which anti-tetanus serum has been used more and more freely sincethose days, some 50 or more people still die from tetanusin this country each year. Most of these infections

probably arise as the result of injuries so trivial that theyare not seen by a doctor, so that the injured have nochance of protection by passive immunity. It seemstherefore that this annual loss of life can be substantiallyreduced only by the wider use of active immunisation.The protection afforded by tetanus antitoxin lasts

only about two weeks ; and in persons who have hadantitoxin on a previous occasion it may be eliminatedfrom the body abnormally rapidly and no appreciableprotection may be conferred. Fortunately, we can givemuch more lasting protection by active immunisation.Since whole armies can be immunised before facingconsiderable risks of injury, it is natural that much of ourinformation about active immunisation should come from

military sources. 7 It is largely as the result of war

experience that successful methods have been established.Two doses of tetanus toxoid, at an interval of six weeks,followed by a third dose six months later, confer adequateimmunity for five years. Booster doses are best givenevery four years. After an injury a further dose oftoxoid stimulates the defences sufficiently to make theadministration of antitoxin unnecessary unless treatmenthas been delayed for more than twenty-four hours afterinjury.a Both the British and United States armies usedroutine immunisation during the late war ; and immu-nisation was compulsory for American soldiers. Theincidence of tetanus was reduced to 1/25 of the 1914-18rate in the British Army ; and among American troopsthere was only 1 case of tetanus among all battle casual-ties. Tetanus antitoxin was given to British wounded,

but the Americans used no antitoxin, giving their injureda booster dose of tetanus toxoid. After a break from1945 to 1949, active immunisation has been a routineprocedure in the British Army, so that there is a sectionof the community-men who have done their NationalService-with an adequate basal immunity. But the restof the civilian population are poorly defended. Mostdeaths from tetanus occur in the 5-14 age-group andthere is therefore much to be said for immunising childrenwhen they go to school. Combined diphtheria-tetanusimmunisation of children has been compulsory in Francesince 1940, and nearly all Danish children are similarlytreated.9 9 In the United States and Canada diphtheria-tetanus immunisation, often combined with whooping-cough vaccination, is widespread. The child enteringschool at 5 might well receive a booster dose of diphtheriaprophylactic combined with the initial dose of tetanustoxoid. But, since basic immunity to diphtheria willalready have been established in many of these children,the secondary response to the diphtheria toxoid mightwell swamp the antigenic response to tetanus toxoidunless the composition of the combined prophylactic weresuitable ; so careful inquiry into the effect of variousprophylactic combinations would be needed before sucha scheme could be adopted.

It is not easy to envisage immunisation of the wholeadult population, although those most at risk might wellbe offered protection. Agricultural workers, especiallythose in eastern and south-western England, labourers,stable hands, and mechanics are all prone to injuriescontaminated with earth. But so are pedestrians,cyclists, and drivers on our roads ; and that includesalmost everybody. Nevertheless, in a generation’s timethe toll of tetanus would be much reduced if expectantmothers and children entering school were added toNational Servicemen as priority candidates for tetanusimmunisation.

9. Scheibel, I. Bull. Wld Hlth Org. 1955, 13, 381.10. Copeman, W. S. C., Ackerman, W. L. Quart. J. Med. 1944,

13, 37.11. Copeman, W. S. C., Pugh, L. G. C. Lancet, 1945, ii, 553.12. Copeman, W. S. C. Brit. med. J. 1949, ii, 191.13. Baker, D. M. Ann. rheum. Dis. 1955, 14, 385.

MENOPAUSAL PANNICULOSIS

A FEW years ago Copeman and his colleagues 10 11gathered evidence to show that " the fat tissues of thebody are subject to pathological variations which causepain." They were investigating the common syndromesof " fibrositis " and " rheumatic " pain, and they sug-gested that, in certain cases at least, the characteristicpain originates in areas of local oedema of the fibro-fattysubcutaneous tissues, particularly in the residual fatareas of the back. Their post-mortem dissections andbiopsy studies of the back in fibrositis showed that thepalpable painful nodules were often identifiable as

oedematous fat lobules. Their view of the origin of thepain as a local tension oedema was supported by theirfinding that induction of a state of clinical dehydration(again in selected patients) brought relief of pain to asignificant proportion. Copeman 10 12 has suggested asimilar cause for the type of fibrositic pain that occursin panniculitis, a condition frequent at the age of themenopause, in which the panniculus adiposus increasesin bulk in certain characteristic regions of the limbs andback, producing pain and tenderness. He believes thatalso in this syndrome the underlying mechanism is ashift of extracellular fluid into the fatty tissue cells.

Baker 13 has recently studied panniculitis (she prefersthe term " panniculosis ") by means of skin biopsies in49 cases. The biopsies showed no apparent abnormalityof the subcutaneous fat, apart from increased bulk ; but80% of them showed an increased depth and density ofthe collagen layer of the skin, though the fibres themselveswere mature, acellular, and morphologically normal under