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of working, and 460 of these (344 men and 116 women) werein full-time jobs. A further 23 (11 men and 12 women) wereworking part-time, and a further 72 (53 men and 19 women)were unemployed. In the full-time group 3 men had positivesputum, and 16 were in unsuitable occupations. In the

part-time group all were sputum-negative and had suitablejobs. In the unemployed group, 21 men and 3 women hadpositive sputum. These 3 women and 5 of the men were not

really fit for any work, but the other 16 men could well havebeen employed in a sheltered workshop, had one been avail-able ; and most of the remaining 32 in this group wouldhave benefited from retraining.

Dr. Marsh suggests that, if his figures are representativeof the whole country, we must need sheltered workshopsfor 2510 sputum-positive men, and retraining schemesfor a furthei 3780 patients with closed tuberculosis. Ifwe are to eradicate this disease we must, he thinks,accept the fact that training centres can only be run ata loss. Sputum-positive patients must be kept awayfrom their fellow workers-in municipal sheltered work-shops employing a small number of men, and in moresmall factories of the Remploy type. Some adequateform of family allowances would help to ensure the goodnutrition of the tuberculous wage-earner’s family, andto protect them from infection. What are we preparedto do for a patient until he becomes non-infectious And what will we do to maintain his welfare and oursif he cannot be made non-infectious ’? These are thecrucial questions ; and in Dr. Marsh’s view we are notyet finding effective answers to them.

THE PAINFUL INJECTION

THE increasing popularity among clinicians of the

parenteral route for administering drugs is not matchedby corresponding enthusiasm among the recipients.Dr. Janet Travell found that among professional peoplewhom she questioned 99% had had one or more hypo-dermic injections, and of these only about 10% said theydid not dread the next one.

Travell disagrees with the common opinion that somepain is to be expected from the mere jab of the hypo-dermic needle : with a non-irritant solution a hypodermicinjection can be painless. Immediate pain is due to :

(1) local irritation from the antiseptic or the parenteralsolution ; (2) mechanical trauma from the needling orthe sudden distension of the tissues by the rapid intro-duction of fluid ; or (3) abnormal sensitivity, either ofthe skin or the underlying muscle, at the site of injection.Counter-stimulation, by pinching or slapping the skin justas the. needle is inserted, may distract the patient’sattention from the prick ; but the most convenientmeasure to eliminate skin pain is the application of cold.Nerve conduction is blocked when the temperature fallsto about 10°C. Intermittent application to the skin ofan ice-cube for a few minutes before the injection isefficacious, but a refrigerant spray of ethyl chloride orone of the halogenated hydrocarbons is more reliable.The spray need be applied only for two or three seconds ;and’ recovery of sensation is correspondingly rapid, so

the skin should be cleansed beforehand and the syringebe handy for immediate injection. Travell gives threerules for eliminating cutaneous pain : (1) use a sharpneedle, with no barbs, which has the smallest diametercompatible with the viscosity of the injection solution ;(2) allow a volatile antiseptic, such as alcohol, to evaporatefully before making the injection ; (3) apply a coolingspray to the site for two or three seconds and insertthe needle directly the liquid has evaporated from theskin.

Severe subcutaneous pain is due to the needle enteringand pulling on the fascia of the underlying muscle. The

injection solution should be buffered and isotonic, andat room or icebox temperature.

1. Travell, J. J. Amer. med. Ass. 1955, 158, 368.

Venous pain is minimised if the course of the veinand its patency are accurately determined beforehand.If the injection solution is a-local irritant, it should be

injected slowly, so that it is diluted by the blood-stream ;slow injection also gives the patient time to warnthe doctor promptly if the solution leaks outside thevein.

Muscular pain results from injection into a hyper-sensitive area of muscle. These spots of deep hyperalgesia(" trigger areas ") may be recognised by careful palpa-tion, which reveals deep tenderness, referred pain, andhypercontractility. With practice, the trigger area isfelt as more resistant than the surrounding normal muscle.Normal muscle is practically insensitive to dry needling ;but an irritant solution may cause pain, unless a localanaesthetic is incorporated in the injection fluid. Travellalso urges caution in using for intramuscular injectionany region of the body that has been the seat of a

severely painful state, such as acute bursitis with calci-fication. It is best to inject into the mid-portions of thedeltoid or gluteus-maximus muscles. If by chance themuscle twitches or pain is felt on insertion of the needle,this should be withdrawn from the muscle but not out ofthe skin, and redirected into a non-tender area ; andthe solution should always be injected slowly.The attention to detail recommended by Travell would

seem to be eminently worth while for both doctorand patient.

HYPNOSIS FOR THE BURNED

AMONG those who treat burned patients opinion is stilldivided on whether the patient should be anaesthetisedduring local treatment. In many clinics morphine anal-gesia alone is used, while in others the procedure variesfrom simple nitrous-oxide/oxygen analgesia with theaddition, if need be, of ether, to administration of relaxantdrugs and endotracheal intubation. By means of hyp-nosis Crasilneck et a].’ have successfully relieved pain in6 out of 8 patients during initial local treatment andsubsequent dressings and skin-grafting; and these

hypnosis patients were induced to eat much more.Once the dangers of fatal oligaemia due to plasma loss

and of infection have been surmounted, the greatestproblem in the severely burned is that of nutrition.Patients with deep burns lose much protein in the exudatefrom the granulating areas, and this, coupled with theusually poor consumption of food, leads to severe wastingof muscle and fat. In this " katabolic " state skin-graft-ing, autogenous or homogenous, seems to be less successfulthan when nutrition is good and the patient is in an" anabolic " state. Attempts have been made to improvethe nutritional state of burned patients by intravenousfeeding with amino-acids, calories being provided byinfusion of glucose and other- sugars and fat emulsions ;but intravenous feeding of this kind, besides beingexpensive, is liable to impair appetite and so reduceoral consumption of food, and the utilisation of theamino-acids is uncertain. Repeated infusions of plasmaare dangerous, and unless accompanied by non-proteincalories are nutritionally unsound. Large amounts ofcalories and protein have been administered successfullyby instilling homogenised food through an indwellingnasal tube into the stomach ; but this method is liable tocause nausea when administration is intermittent or

diarrhoea when it is continuous, and some patientsfind it difficult to tolerate an indwelling tube for

long.By hypnotic suggestion Crasilneck et al. increased the

daily intake to over 7000 calories in 3 patients andmaintained a large intake for twelve days. Not onlywas the total quantity of food increased, but individualdislikes for particular foods were overcome and a selective1. Crasilneck, H. B., Stirman, J. A., Wilson, B. J., McCranie, E. J.,

Fogelman, M. J. J. Amer. med. Ass. 1955, 158, 103.

548

intake of suitable food could be specifically suggested.The pathetic physical and mental state to which a

previously healthy young man can be reduced by thepain, partial starvation, and tissue wasting accompanyingthe sloughing and granulation of extensive burns presentsa therapeutic problem to which there is still no certainsolution. Much quicker progress has resulted from earlierexcision and grafting, often with donated skin, and theensuing reduction in the extent of the granulatingsurface ; and the account by Crasilneck et al. stronglysuggests that hypnosis may be a valuable further aid.Against the more general clinical use of hypnosis it hasbeen said that some patients are not amenable, that it isexpensive of the psychiatrist’s time, and that it can beapplied only by the highly trained.2 Crasilneck et al.are not impressed by these objections. Of the 8

patients they treated 6 were suggestible ; and only anhour and a half was required to obtain initial rapport,while the subsequent inductions took only a few minutes.Suggestion was reinforced by brief daily episodes, andrapport could be transferred to the surgeon after only afew visits. Further trial of this method should, if

possible, be combined with controlled observations of itseffects on the metabolic disturbances.

D.N.A. AND NUCLEOPROTEIN

CYTOLOGICAL, chemical, and genetic researches all

point to a close relation between the genetic functionsof the cell and the desoxyribonucleoprotein contained inthe cell nucleus. Since the protein moiety may be assimple a structure as a protamine, the complexity neces-sary in the genetically active system doubtless resides inthe desoxyribonucleic acid (D.N.A.) molecule. Perhaps thebest-known example of a genetic change initiated byD.N.A. is in the transformation of Pneumococcus II B (anattenuated non-encapsulated organism forming roughcolonies) to Pneumococcus III S (an encapsulated strainforming smooth colonies) by minute amounts of extractsof the III S strain. This extract had all the properties ofa D.N.A. and appeared free of other materials such asbacterial polysaccharides.3 The chemical and physicalstructure of the D.N.A. macromolecule is therefore offundamental importance. It has long been known thatthe macromolecule is in the form of a long fibre built upof essentially simple mononucleotides, each mononucleo-tide consisting of a heterocyclic base (for the most partadenine, guanine, cytosine, or thymine) linked to a sugar(desoxyribofuranose) bearing a phosphoric-acid residueon its terminal hydroxyl group. The macromolecule isbuilt up by one of the free phosphoric-acid groups of onemononucleotide being esterified to the free hydroxylgroup in the sugar ring of another mononucleotide, andso on.4 The elucidation of the exact sequence of some3000-30,000 mononucleotides in a macromolecule witha molecular weight 5 of the order of 106 to 107 is not

likely to be achieved, but the over-all picture of themolecule is becoming clearer and the structure suggestedseems capable of explaining many of the physical,chemical, and biological data.As long ago as 1938 X-ray diffraction photographs of

fibres of D.N.A. were found to show evidence of crystallineform, there being proof of a regularly repeated unit inthe macromolecule occurring every 3.4A.6 But morerecently it was shown that if a needle-point is slowlywithdrawn from a viscous gel of sodium desoxyribo-nucleate in water under conditions of controlledhumidity, fibres are produced which give two distinct2. Wolberg, L. R. Medical Hypnosis. New York, 1948; vol. i.3. Avery, O. T., MacLeod, C. M., McCarty, M. J. exp. Med. 1944,

79, 137.4. Gulland, J. M., Jordan, D. O., Taylor, H. F. W. J. chem. Soc.

1947, p. 1131.5. See Jordan, D. O. In The Nucleic Acids. Edited by E. Chargaff

and J. N. Davidson. New York and London, 1955; vol. I,p. 470.

6. Astbury, W. T., Bell, F. O. Nature, Lond. 1938, 141, 747.

types of X-ray diagrams,7 the one highly crystalline(structure A) and the other paracrystalline (structure B)with a lower degree of regularity. These two struc-tures are normally interconvertible and differ in degreeof stretching and of water content. Crystallographicanalysis’ of these diffraction patterns 7 and of the

crystal structure of the simple constituents 9 have led tothe suggestion that the macromolecule is a double helicalstructure-two paired chains of nucleotides each coiledround a common axis.IO (A helical type of structure, sosuccessful in explaining protein structure, had been

suggested previously,11 but the details had been severelycriticised.) The phosphoric-acid residues lie on the out-side, and the heterocyclic bases on the inside of thehelix. The individual nucleotides are 3.4A apart and thestructure repeats its coil every 34A. Each chain is heldto its partner by hydrogen bonding between adjacentpairs of heterocyclic bases, and consideration of molecularmodels shows that the only permitted pairing is betweenadenine and thymine, and between guanine and cytosine.This accords with published data on the base content ofD.N.A. isolated from widely differing biological materials.These analyses have shown that the molecular propor-tion of adenine is always equal to that of thymine andthe molecular proportion of guanine was always equalto that of cytosine.12Any structure for a genetic material must be able to

suggest how the material can be accurately duplicatedwithin the cell to account for inheritance characteristics.Previous suggestions had rested mainly on a templatetype of hypothesis, but the double helix immediately

suggested another, more likely, mechanism." In theintact double helix, whenever adenine occurs in one

chain thymine must occur in the other, and vice versa;and similarly for guanine and cytosine. Before the newsynthesis of D.N.A. occurs (which, incidentally, appearsto take place some time before cell division 14) thedouble chain might uncoil and then, a pool of precursorsbeing available, each separate strand could build upanother chain of exactly the same configuration as itsoriginal partner since only the same hydrogen bonding ispermitted. The proposed double helix is an open struc-ture, so there is ample room for a polypeptide to coilround the same axis, and in the proposed model thephosphoric acid residues occur at intervals of 7-lA—adistance close to the repeat of a fully extended poly-peptide chain. A possible explanation of spontaneousmutations might be that one of the heterocyclic bases inthe newly formed genetic material occurred in a differenttautomeric form. In an extension of this work 15 someof the dimensions first proposed have been slightly altered,and further characteristics of the proposed structure havebeen suggested.

7. Wilkins, M. F. H., Stokes, A. R., Wilson, H. R. Ibid, 1953,171, 738.

8. Franklin, R. E., Gosling, R. G. Ibid, p. 740; Ibid, 1953, 172,156 ; Acta cryst., Camb. 1953, 6, 673, 678.

9. Furberg, S. Nature, Lond. 1949, 164, 22 ; Acta cryst., Camb.1950, 3, 325.

10. Watson, J. D., Crick, F. H. C. Nature, Lond. 1953, 171, 737.11. Pauling, L., Corey, R. B. Ibid, p. 346.12. See Chargaff, E. In The Nucleic Acids. Edited by E. Chargaff

and J. N. Davidson. New York and London, 1955; vol. I,p. 352.

13. Watson, J. D., Crick, F. H. C. Nature, Lond. 1953, 171, 964.14. Pelc, S. R., Howard, A. Exp. Cell Res. 1952, suppl. 2, 269.15. Feughelman, M., Langridge, R., Seeds, W. E., Stokes, A. R.,

Wilson, H. R., Hooper, C. W., Wilkins, M. H. F., Barclay,R. K., Hamilton, L. D. Nature, Lond. 1955, 175, 834.

THE INDEX and title-page to Vol. I, 1955, which wascompleted with THE LANCET of June 25, is now inpreparation. A copy will be sent gratis to subscriberson receipt of a postcard addressed to the Manager ofTHE LANCET, 7, Adam Street, Adelphi, W.C.2. Sub-scribers who have not already indicated their desireto receive indexes regularly as published should do sonow.