33
had to " matching "-indeed, of the two procedures,this is the more important. Yet even with the employ-ment of universal donors and preliminary matchingdangerous reactions and even deaths have been
reported. In these cases it has been plausibly.suggested that the evil results were due to the hightitre of the donor’s agglutinins. Usually the recipient’splasma dilutes these to such an extent that they arenegligible, but if the titre either of the donor’s agglu-tinins or of the recipient’s agglutinogens is unusuallyhigh this may not happen. Cross-matching willreveal the possibility of this danger, but not thecertainly of its presence.As a general rule it may be taken that a donor
of the same group as the recipient is safe, but groupingwithout matching should never be relied upon. Inany case it should not be forgotten that the selectionof donors demands the utmost care and considerableexperience, and should never be lightly or hurriedlyundertaken. Even when all possible-precautions inthe selection of the donor have been observed it iswell to perform the " biological test "-that is, tointroduce 5 c.cm. of the selected blood and then waitfive minutes and watch the effect on the patient.
THE RITUAL OF THE WET SHEET
IN an address published in Folk Lore last June,lMiss M. E. Durham argued that many of the devicesadopted by primitive man to prevent his dead fromreturning as ghosts were really safeguards againstinfection. Purification rites performed by the rela-tives included bathing in sea-water, or remainingin seclusion for a time, while sometimes the bodywas ferried across a river to burial. But these andsimilar measures were often distorted until theybecame pointless, and such a decline is illustratedin the story of the carbolised sheet, as learnedly toldby Dr. John Ritchie 2 of Dumfries. The custom is
passing, but it is still not uncommon to see a sheetsoaked in antiseptic hanging outside the door ofthe room in which a patient with an infectious diseaseis being nursed-the theory being that the scarlatinalstreptococcus and his colleagues turn pale at theodour of carbolic, and rather than cross the thresholdprefer to remain prisoners in the sick-room. Savageraces, it seems, share this belief that infection canbe checked by physical barriers, and they blocktheir village paths with thorn twigs to keep out thedevil of disease. There is some sense, indeed, in this,for if thorns cannot keep out spirits they may welldeter a carrier of infection. Dr. Ritchie remindsus that during the Plague of 1603 when a Londonerdied in a country town no one could be found tobury him, and " every one," as Thomas Dekkernoted, " with bag and baggage marcht home, barri-cadoing their dores and windowes with firbushes,ferne and bundles of straw to keepe out the pestilenceat the staves end." These precautions at least pre-vented the plague-stricken passers-by from breathinginfection into their neighbours’ faces " in spite," asPepys tells us they were ready to do in his day.The carbolised sheet of modern times is by no meansso effective an obstruction, but as a matter of factit originally had another and more satisfactoryfunction. In early times cold water was used to coolthe air of the sick-room, both by the methodistsat the beginning of the Christian era, and by physi-cians of the Arabian school who, believing that hotdry air was a cause of disease, hung the walls of theroom with wet sheets and spread cooling herbs andflowers on the floor. Later, in the time of the Black
1 See See THE LANCET, 1933, ii., 570.2 Caledonian Med. Jour., 1933, xv., 155.
Death, it was still held that hot dry air must be cooledand moistened, and attempts were made to purifyit by adding vinegar to the water in which the wallsheets were soaked. Thenceforward the belief thatair could be disinfected continued to gain ground,and many substances have been credited with powerto neutralise the miasma emanating from the patient.The contagion of typhus was said to be destroyed bythe fumes of nitrous acid, and the same result wasexpected from chloride of lime spread upon thefloor-a sad decline, surely, from the herbs andflowers of less civilised times. Even to-day the airof the sick-room is often sprayed with disinfectants,and no doubt they cool it as pleasantly as the wetsheet of the past. But the sheet itself, robbed of itsoriginal function, has migrated outside the door,and become a symbol to warn away the healthy ;just as (Dr. Ritchie tells us) a " quhyt claith " wasonce hung upon the doors of Scottish houses to warnneighbours of the pestilence. The change of situationprovides a good example of the degeneracy of soundpractice into more or less useless ritual.
EXCRETION OF HORMONES IN MIGRAINE
FROM being classed as a vaguely elegant afflictionand left at that, migraine has during the last 20years become the subject of laborious research. Ithas been studied in relation to epilepsy,. cerebralvascular lesions, paroxysmal tachycardia, endocrinedisturbance, the vegetative nervous system, and
allergy ; the sella turcica has been accused of causingits headaches by compressing the pituitary duringperiods of physiological enlargement; abdominal
migraine has been recognised, psychic equivalentshave been conceded, and the pressure of the cerebro.spinal fluid has been measured during attacks, withcontradictory results. Recent work by Riley,Brickner, and Kurzrok indicates a relationshipbetween migrainous attacks and the abnormalsecretion of prolan in the urine. Whereas theelin(the oestrus-producing hormone, also known as
oestrin, folliculin, or progynon) is normally found inthe urine throughout the menstrual life of women,prolan (an anterior pituitary gonadotropic hormoneor something akin to it) is normally absent except inpregnancy and after the menopause. Riley and hiscolleagues found that in the urine of migrainouswomen theelin was usually absent or reduced inquantity, while the attacks of migraine were nearlyalways preceded by the appearance of prolan in theurine. Results pointing in the same direction havenow been obtained by three French observers,P.-L. Drouet, L. Mathieu, and L. Collesson,2 who haveexamined pituitary function in migraine by injectingfrogs with samples of urine from migrainous patientsand observing changes in pigmentation. Drouet,working with Prof. R. Collin, had previously usedthis method of estimating pituitary function inGraves’s disease and cases of pituitary tumour; thetest depends on the presence of a melanophore-dilatorin the secretion of the posterior and perhaps the otherlobes. The same substance causes dilatation of the
erythrophores of a minnow, Phoxinus laevis, andDrouet and his co-workers have used this action toconfirm their results in some cases. Altogether, theyinjected 624 frogs with 312 samples of urine, and 39minnows with 9 samples of urine which had pre-viously given a positive melanophore reaction in frogs.They found that the pituitary hormone causing these
1 Bull. Neurol. Inst. New York, 1933, iii., 53; see THELANCET, 1933, i., 1141.
2 Bull. et mém. Soc. méd. hôp. de Paris, Dec. 18th, 1933,p. 1485.
34
pigment changes appeared in the urine of 12 out of 14migrainous patients at the times of the attacks. Thehormone might be present for a period lasting fromone to ten days ; its appearance in the urine wasnot always rigidly synchronous with the attack, butsometimes preceded or followed the onset of headache ;in some cases, again, the hormone disappeared at thecrisis of the attack and reappeared for a time as itsubsided. Between the attacks the urine of these
patients gave negative melanophore reactions. In2 cases out of the 14 no positive reaction was everobtained, though clinically these resembled the others.The observers conclude that in 12 cases of theirseries there was hypersecretion of a hormone believedto be derived from the posterior lobe of the pituitary,and that this was probably accompanied by over-activity of the whole gland. They regard their
findings as evidence, at all events, of a physiologicaldisturbance of the pituitary during attacks of migraine.Unfortunately they give no details of their technique,and the reader is left wondering what substancesother than pituitary hormone will cause a frog tochange colour or bring a blush to the skin of PhoxinusZcevis.
THE TREATMENT OF SUBACUTE COMBINEDDEGENERATION
THE discussion on the treatment of subacutecombined degeneration of the spinal cord, at a jointmeeting of the sections of neurology and of thera-peutics and pharmacology at the Royal Society ofMedicine on Dec. 21st, revealed general agreementon the value of adequate treatment, but much differ-ence of opinion as to what form treatment shouldtake. Even more divergent were the views expressedon the criteria necessary for diagnosis and the natureof the lesions. Dr. E. A. Carmichael and Dr. C. C.Ungley maintained that the signs must be bothbilateral and objective. The blood picture must beof the pernicious type, and a typical reticulocyteresponse to liver therapy must occur, and there mustbe complete achlorhydria to histamine stimulation.In Dr. Carmichael’s experience subacute combineddegeneration in patients under 40 was rare; Dr.
Ungley had met with typical cases at an earlier age.Others taking part in the discussion were prepared toaccept far less stringent criteria of diagnosis. Prof. F.
Langmead and Dr. Wilfred Harris suggested thattoo much emphasis may have been laid in the pastupon the exact character of the anaemia, holdingthat in general nervous symptoms associated withanaemia respond dramatically to large doses of ironalone. Neither of the speakers adopting the morerigid criteria of diagnosis had failed to find anyresponse to massive iron therapy, but they agreed thatthe response to liver, especially in the form of intra-muscular extracts, was extremely satisfactory; Dr.
Ungley thought that possibly extracts prepared bypressure were more satisfactory than those extractedby process. Dr. L. J. Witts pointed outthat equally satisfactory results had been obtained withstomach preparations ; he quoted J. F. Wilkinson’slarge series of patients with pernicious anaemia, noneof whom had developed cord symptoms, though theyhad received stomach extract only.
E. Meulengracht 1 has recently reported that inhis hands stomach extracts are at least as effective asliver in the treatment of cord lesions. It seems
probable that as long as the red cell count is main-tained above 5,000,000 per c.mm. cord lesions arenot likely to develop, and that treatment that will
1 Klin. Woch., 1933, xii., 1163 ; Ugeskrift for Laeger, 1933,xcv., 819.
raise the blood count to this level will improve thenervous symptoms. There is as yet no convincingclinical, as opposed to experimental, evidence thatcord lesions can be relieved independently of theblood picture. Prof. E. Mellanby described at thediscussion an interesting group of animal experimentsin which he had been able to produce lesions in thecord not unlike those of subacute combined degenera-tion by feeding a diet poor in vitamin A ; the additionof vitamin A to the diet prevents the appearance ofthe lesions, also whole liver and its fat-soluble content,but not the ordinary liver extracts effective inpernicious anaemia. Though making no claim to.have produced experimentally spinal cord degenera-tion exactly similar to subacute combined degenerationin man, Prof. Mellanby suggested that its study might.throw light on the aetiology of this lesion, which maybe related to, but in some essential ways differentfrom, that of pernicious anaemia. The blood changesinduced in MiU!U)uimlu are relieved by a water-soluble Mfactor present in whole liver, the experimental lesionsonly by a fat-soluble factor. In view of theseobservations it is disappointing that both Carmichaeland Ungley have found vitamin A useless in thetreatment of subacute combined degeneration in Ban.
In the course of the discussion Dr. Carmichaelbrought forward interesting observations on the
changes in sensory nerves. He was able to demon-strate that great loss of myelin in sensory nerves is astriking feature, a fact which has been known forsome time, but has hardly received the attention itdeserves. In his view the recovery that occurs afteradequate treatment is largely due to recovery of
sensory nerves and not of cord lesions.
THE NATURE OF FILTRABLE VIRUSES
THE claim to have demonstrated that a filtrablevirus is inanimate is not a novel one, and in theirobservations on tobacco mosaic disease E. Barton-
Wright and A. M. McBain 1 are dealing with a viruswhose animate nature has already been called in
question by the work of Vinson and Petre in America.It may be that (as they believe) this virus is an
unorganised thing ; on this it is well to keep an openmind. But there are two points, germane to the
controversy over the nature of viruses, which aresometimes overlooked. The first concerns the inadvis-
ability of generalising from observations made onone virus only. Barton-Wright and McBain makeno such generalisation, but others may be temptedto do so for them. There is no good reason forsupposing that all filtrable viruses are of the samenature ; in fact, in the case of the animal viruseswe have evidence that this is not so ; the viruses ofbovine pleuro-pneumonia and agalectia differ obviouslyfrom the rest. The second point concerns the diffi-culty of proving that a virus is inanimate. Leavingaside the filtrable viruses it is generally agreed thatthe causal agents of infective processes are livingorganised things. In the absence of proof to thecontrary it is reasonable, therefore, to assume thatall infective processes are caused by living agents,and those investigators who wish to prove this untruewill have to advance very solid proof if they are toconvince. The short note published by Barton-Wright and McBain contains little detail, but putbriefly their claim rests on two observations. Froma purified (phosphate eluate) virus suspension theyhave obtained two fractions, one a protein and theother a white crystalline solid. Both were virulent,and the crystalline material, when purified by repeated
1 Nature, Dec. 30th, 1933, p. 1003.