925

Those concerned in insulin production have thus

escaped the criticisms made in previous reports by thecommission, for example those on dental goods whereelements of exclusive dealing and collective boycottwere brought to notice.Monopoly is a word of some emotional content ; the

Left may employ it against Big Business in privateenterprise, the Right against nationalised industries.Whatever the political implications of the matter, thereport is of general interest. The testimony upon whichit is based includes evidence from 16 selected hospitalswith diabetic clinics. The survey which section 7 of theAct requires the commission to undertake describes thestrength and kinds of insulin and the processes of produc-tion. We are given a brief history of the discovery of thedrug, its introduction into the United Kingdom, and itssupply during the separate periods of 1923-27, 1928-40,and 1941-50. As diabetes mellitus is not a notifiabledisease, no exact statistics are available, but the reportestimates that there are 200,000 diabetic patients in theUnited Kingdom and that 60-70% of them receiveinsulin. Retail chemists distribute 80% and hospitals20%. There is a short history of the legislation on thesubject, mentioning the Therapeutic Substances Act,1925, and its regulations, the Poisons Rules made underthe Pharmacy and Poisons Act, 1933, and the FinanceAct, 1934, when Neville Chamberlain freed importedinsulin from duty. Naturally, however, the most materialfinding of the commission is their reassuring declarationthat the present arrangements do not operate againstthe public interest and their refusal to recommend thatthey be discontinued.

1. Hirst, G. K. J. exp. Med. 1942, 76, 195. 2. Anderson, S. G. Aust. J. exp. Biol. med. Sci. 1948, 26, 347.3. Gottschalk, A., Lind, P. E. Nature, Lond. 1949, 164, 232.4. Gottschalk, A. Ibid, 1951, 167. 845.5. Tamm, I., Horsfall, F. L. jun. Proc. Soc. exp. Biol., N.Y. 1950,

74, 108.6. Gottschalk, A. Nature, Lond. 1952, 170, 662.7. Odin, L. Ibid, p. 663.

INFLUENZA-VIRUS MUCINASE

IN his early descriptions of agglutination of red blood-cells by influenza virus, Hirst 1 divided the reaction intotwo stages—first, adsorption of virus to red cells and,secondly, elution of virus from the cells. The adsorptionappeared to be predominantly physicochemical, butHirst noted that the elution bore many of the marks of

an enzymic reaction. Detailed studies, notably by Burnetand his colleagues in Melbourne, have supported Hirst’soriginal observations ; and influenza virus has beenfound to act in enzymic fashion on soluble inhibitors ofvirus agglutination.2 In 1949 Gottschalk and Lind 3

showed that interaction of influenza virus with solubleinhibitor produced a dialysable split product, whichGottschalk 4 later characterised as an N-substitutedfructosamine.

Early work on the soluble inhibitors was carried outwith materials, such as ovarian-cyst mucoid or ovomucin,which are not always to be had in large enough amountsto satisfy the avid requirements of the biochemist.Tamm and Horsfall 5 showed, however, that humanurine contains a potent inhibitor of influenza-virusagglutination ; and Gottschalk 6 and Odin 7 have analysedthis inhibitor. Gottschalk 6 found that after hydrolysisgalactose, mannose, and fucose were present along witha hexosamine base, which on chromatographic evidenceseemed to be a mixture of glucosamine and galacto-samine. The smallest carbohydrate unit in the muco-protein was estimated to have a molecular weight of(2500)n, where n is not more than 3 or 4. This carbo-hydrate unit is regarded as a prosthetic group conju-gated to protein ; about two hundred such groupsattached to each protein molecule make a mucoproteinmolecule. In addition to the sugars already mentioned," sialic acid " was detected in the urinary inhibitor. This

monobasic reducing acid, whose structure is still unknown,is found in many inhibitory substances, although in pureform it has no inhibitory activity. " Sialic acid " hassimilar properties to Gottschalk’s 4 split product and isprobably an important clue to the chemistry of theseinhibitors.The viruses belonging to the influenza/mumps/New-

castle disease/fowl-plague group, which all show mucinaseactivity, are the only ones where an intrinsic enzymicreaction has been clearly proved. Yet a mystery remainsto trouble the biologist ; of what use is this enzyme tothe virus ? ’I Is it a micro-bulldozer which helps the virusto dig its way through the cell wall ’I Fazekas deSt. Groth 8 cast strong doubt on this possibility whenhe showed that virus particles were taken into cells underconditions where there was no virus enzymic activity.Does the enzyme help the virus to overcome the effectsof the host’s normal inhibitors, as some have suggested ? ‘?This sounds the most attractive hypothesis ; but

although mucoids inhibit agglutination, they rarelyinhibit virus infectivity to any great extent ; and thevirulence of a virus is unrelated to its enzymic activity.Has the enzyme some intracellular function in virus

multiplication ; or is it a vestigial organ, a virusiformappendix, which may have had some useful function atan earlier stage in virus evolution ? At present the factsallow of little more than idle speculation-a pleasantbut often fruitless occupation. ,

8. Fazekas de St. Groth, S. Ibid, 1948, 162, 294,

STANDARD FOR SEDIMENTATION-RATETHE British Standards Institution has now turned its

attention to tubes for estimating the sedimentation-rateof red blood-cells. This attention is timely sinceat present the results of different workers are often notcomparable. The standard textbooks list up to sixmethods of estimating sedimentation-rate. The proposedstandard adopts only two methods : (1) the Westergren,both normal and a micro modification, and (2) theWintrobe. This limitation is certainly sensible in thiscountry, where most laboratories use one or the otherof these two techniques. The tuberculosis departmentsand sanatoria tend to rely on the Westergren method,while the clinical laboratories of general hospitals on thewhole prefer the Wintrobe method.The Wintrobe technique was originally designed so

that the packed red-cell volume-or haematocrit-couldbe determined on the sample of blood that had first beenused for determining the sedimentation-rate ; -, andWintrobe used the haematocrit value to " correct " foranaemia, which increases the sedimentation-rate. Of late

years the validity of this correction has been challenged;but the technique remains a useful and simple one. Bythe original Westergren method the tube had a graduatedlength of 200 mm. and a bore of about 2-45 mm. Such atube needs about 1-5 ml. of blood to fill it, which in adultsis easily obtained by venepuncture. In children, however,venepuncture may not be convenient or desirable, andthe institute’s technical committee has therefore recom-mended in addition a smaller tube of Westergren type.Experiments showed that the bore of the tube must beat least 1-5 mm. ; so the committee proposes the adoptionof a tube with a graduated length of 100 mm. and abore of 1 65 ±0-15 mm., which can be filled with only0-25 ml. of blood.The standard specifications seem unexceptionable-

except for the micro Westergren tube they correspond totypes already in use-and they ensure minimal variationof tube-length, tube-bore, and, in the Westergren tubes,size of the lower orifice. Truly comparable results shouldtherefore be obtained with these tubes.The committee, recognising the importance of proper

stands, propose patterns for the three types of tube.They also give valuable instructions for cleaning the

926

tubes. The British Standards Institution asks thatcomments on this draft standard should reach its officesat 24, Victoria Street, London, S.W.l, not later thanNov. 27.

DICKENS AND THE DOCTORS

FEW real doctors have ever achieved the stature ofthose concocted by Charles Dickens-though LordWebb-Johnson, after hearing the Lloyd-Roberts lectureat the Royal Society of Medicine on Oct. 29, tried tomake out a case for Lloyd-Roberts himself. The meetinghad just had the felicity of hearing Mr. Bernard Darwinon " Dickens’s Doctors " ; and- if they had not knowntheir luck from the start they would have been broughtto a proper sense of it by a reminder from Dr. F. M. R.Walshe, F.R.S., the president, that the first three Lloyd-Roberts lectures were on defects of man’s structure,racial degeneration, and criminal law and insanity.

Mr. Darwin was somewhat hampered by the richnessof his material : we can almost fancy the vast companyof doctors on the Dickensian Medical Register a-cockingtheir medical eyes in an attempt to catch his. Dickensknew more about medicine than the average layman,though a trifle weak on spontaneous combustion. Helaughed at doctors, but he liked them too ; as we maybe sure, Mr. Darwin thinks, from the fact that he hadno murderers among them-despite the fact that Dr.William Palmer was at the height of his poisoningpractice at about the time he was writing. Many of hisdoctors are anonymous ; and some are spurious, likeDoctor Marigold (who was christened after the physicianwho produced him), or unqualified, like Mr. AlfredJingle (who asserted that he had saved the life of afemale, who had taken prussic acid, by means of a stomach-pump which he happened to have in his portmanteau) ;and one was a marionette who had trouble with hiswires, and delivered his opinions into the air. Butamong the regular practitioners Dickens had a splendidrange, from Sir Tumley Snuffin and Sir Parker Peps(the only two doctors he ever knighted), to poor Mr.Chillip who preferred darkness and draughts to theformidable company of Miss Trotwood, when DavidCopperfield was on the way. That dull dog AllanWoodcourt in Bleak House reminded Mr. Darwin ofa don whom he had once asked for an opinion of a deadcolleague : " He replied with incredible venom, Ohyou couldn’t possibly dislike him.’ " Then there was thatsplendid humbug Mr. Jobling, M.R.C.s., who examinedpatients for the Anglo-Bengalee Insurance Company,and had a way of smacking his lips and saying " Ah !

"

Dr. Manette in A Tale of Two Cities, with his compulsivereversions to shoemaking, is perhaps more interestingas a patient than as a doctor ; and the doctor in SamWeller’s story of the patient who died on principle is

mainly notable, Mr. Darwin thinks, for his courageousreadiness to admit he did not know how many crumpetswould prove fatal. But the doctors whose companyhe particularly favours are Bob Sawyer of Guy’s andJack Hopkins (who told the story of the rattling finechild who swallowed the necklace) of Barts. Dickenswas so fertile, and so uncertain whether he had writtenenough words to fill an instalment, that he often threwoff a new character just to stop a gap. Perhaps BobSawyer arrived in this way-certainly Sam Weller’slaconic announcement " There’s a couple of sawbonesdownstairs " does not prepare us for this " great creature"(as Chesterton described him). Some find Mr. Sawyernoisy and vulgar, but Mr. Darwin defended him as

though he were a favourite younger brother. He smokedin the street : but today who does not ’f He drank toomuch : and so did Mr. Pickwick. He called waiters bytheir Christian names : but Mr. Darwin knew of respect-able institutions where distinguished members of ourprofession call waitresses by their Christian names.

Perhaps his habit of sending his boy round to leave bottles

of medicine at the wrong houses, and of getting himselfcalled out of church as though to an urgent case, mightbe regarded as infamous conduct in a professional respect;but then he was so ready to be helpful-to bleed alland sundry on the slightest pretext-and so soundon the curative properties of hot punch. Much must beforgiven Bob, and Dickens clearly forgave him, forhe left him-however unbelievablyłtrying the effectsof a little abstinence. Parting wistfully from his nobleand but half-explored theme Mr. Darwin exhorted readersof Dickens in the words of Mr. Toots to his wife : " Do,do endeavour to remember the medical man. If youcan’t, it’s of no consequence ..."

1. Box, N. E. H. Med. J. Aust. 1952, i, 538.2. Bateman, G. H. In British Surgical Practice, London, 1948;

vol. III, p. 282.

BAROTRAUMA

BAROTRAUMA is by no means a new condition, but itsimportance increases as more and more people fly incivil and military aircraft. The ears, paranasal sinuses

, and teeth can all be affected by changes of pressure;and the three types of barotrauma are described byBox in a recent paper.

Otitic barotrauma is a condition in which the ear isdamaged when a difference in pressure exists betweenthe middle ear and the surrounding atmosphere. Itoccurs in aircraft or in caissons, usually when theatmospheric pressure rises during descent, for the normaleustachian tube opens spontaneously during ascent, butnot during descent. The tensor muscles of the palatemust contract to allow air to enter the tympanic cavity,and this can be done by swallowing, yawning, or auto-inflation by Valsalva’s method ; but there comes a

point at which the pressure difference is so great thatthe compressible portion of the tube becomes squeezedby the external pressure, and when muscular action isno longer capable of opening it. One or both ears maybe affected, and the symptoms produced are pain (whichmay be very severe), deafness (usually conductive intype), tinnitus (sometimes of alarming intensity) andoccasionally vertigo. The changes in the tympanicmembrane vary from a slight indrawing, through a

stage of congestion and interstitial haemorrhage, to-actual rupture. Effusions of clear fluid or blood intothe middle ear may give the appearance of bubblesor of a blue bulging drumhead. The ear may be damagedin this way if the tube fails to open because the passengerdoes not know what to do, because he is asleep, or

because of congestion in his upper respiratory tract.Other causes are hypertrophy of the lymphoid tissuein the tube and malocclusion of the teeth. Ideallyflying should be avoided during a severe upperrespiratory infection. Treatment of the establishedcondition consists of introducing air into the middleear either through the eustachian tube or the tympanicmembrane. Box mentions only the first of these, andstates that politzerisation or catheterisation may berequired ; but Bateman 2 recommends simple paracen-tesis of the drumhead as a better method. It can be

performed without an anaesthetic and affords immediaterelief of pain. The small incision heals very rapidly,and is rarely, if ever, followed by secondary infectionof the middle ear. Recurrent attacks of otitic baro-trauma may be due to hypertrophy of the lymphoidtissue of the tube. Irradiation, applied either by externalor local means, has been used in such cases, but theresults are equivocal and the method is not generallyaccepted.The pain of sinus barotrauma is also more pronounced

during descent, and nasal congestion may lead to the" vacuum " type of headache caused by a blocked ostium.Dental barotrauma, on the other hand, usually occursduring ascent. Molars are particularly affected, and thepain is felt most often in recently filled teeth.