2
676 titrating sugar in urine and blood ; Mr. Victor Bonney contributes a paper on the gynaecological aspect of urology ; Mr. Duncan Morison gives an account of experimental work on routes of absorption in hydro- nephrosis, carried out with dyes in the totally obstructed ureter ; Mr. R. Gordon Craig and Mr. R. K. Lee-Brown write on the pyelographic diagnosis of renal tumour, and Dr. Maurice Meltzer, of New York, on the surgical aspects of polycystic disease of the kidney, while Mr. H. Temple Mursell relates the after-history of a case of nephrectomy for polycystic kidney. Other features are notes on interesting cases; urological hints for practitioners, biochemical notes, a copious body of abstracts, and an index medicus. The size of the publication is quarto ; it is printed on highly glazed paper and illustrated with many excellent radiograms, photographs, and drawings. The coloured plate by Mr. Thornton Shiells, illustrating a hydronephrotic kidney with a suprarenal cyst in sagittal section, is an admirable example of litho- graphic work. We wish our new contemporary many happy returns of the day. ____ IMMUNITY TO CANCER. WHEN a small piece of a tumour is inoculated into B I an animal of the same species as that in which it originated spontaneously, the inoculated cells continue to grow and form a new tumour, the host supplying d them with nourishment by means of the new blood- vessels of the stroma which it furnishes. It is possible experimentally to affect an animal in such a way that the inoculated tumour cells do not grow and do not form a new tumour. They remain alive for a few days x and are then absorbed ; they behave, in fact, just as normal tissue transplanted from one animal to another A of the same species. This condition has been described i as " immunity." It can be induced by injecting animals, before the inoculation of tumour cells, with normal tissues of the same species, and it is also induced when a transplanted tumour is made to undergo regression-for instance, by means of radium. When the phenomenon was first discovered 25 years ago, it seemed to have possibilities of thera- peutic application. But exhaustive investigation by workers of the Imperial Cancer Research Fund served to disappoint these hopes. It was found that the blood of an " immune " animal had no toxic or lethal action on the implanted cells. If an animal bearing an implanted tumour was rendered " immune " by the injection of normal tissues, so that a second inoculation failed to take, the tumour inoculated before " immunisation " was not checked in its growth but continued to grow. Moreover, where a malignant new growth had developed spontaneously, injection of normal tissue failed to render the affected animal immune against the successful inoculation of its own tumour, and a spontaneous development of tumours was observed in " immunised " animals. The conclusion was inevitable, therefore, that the condition was not an immunity against cancerous cells, but rather an interference with the process by which the inoculated cells of one animal established themselves in another animal of the same species. It is not an "immunity to cancer " but an " immunity to the transplantation of cancer." Work on this subject up to the year 1913 was reviewed by Dr. W. H. Woglom, of the Crocker Cancer Research Fund of Columbia University, in his book The Study of Experimental Cancer,l and in the March number of the Cancer Review 2 he gives us an account of the further investigations carried out between 1913 and 1928. His paper is a truly monumental contribu- tion to scientific literature and has been prepared with the thoroughness characteristic of its author. The bibliography contains references to more than 600 papers and a study of the text makes it clear that 1 The Study of Experimental Cancer. New York. 1913. 2 Immunity to Transplanted Tumour. The Cancer Review, March, 1929. Dr. Woglom has read almost all of these in the original. Nor is it a dry compilation of observations and conclusions recorded in the literature, for it is severely critical in tone. Of a number of conclusions which are reached the following may be quoted: " Immunity to transplantable tumours is a generalized refractory condition which appears to be entirely unrelated to other forms of immunity... The outcome of inoculation is determined by an interplay between the hostility of the host and the proliferative vigour of the implant, hence an absolute immunity does not exist... Resistance is effective during the first few days following inoculation, but entirely powerless against an estab- lished tumour. Nothing may accordingly be hoped for at present in respect to a successful therapy from this direction." There is, however, an entirely different immunity to cancer which has been disclosed by the recent work of Dr. J. A. Murray and his colleagues. This immunity is directed not against the successful inoculation of cancerous cells but against the transformation of normal cells into cancerous cells. There are systemic factors which determine the susceptibility of an organism to the genesis of cancer. Some aspects of this problem were dealt with by Dr. Murray in the Twenty-fifth Annual Report of the Imperial Cancer Research Fund and their significance was discussed in our columns.3 It is obvious that if further pro- gress along these lines is possible it would be in the direction of preventing cancer rather than curing it. ARTHRITIS DEFORMANS AND ACCIDENTS. IN persons of rheumatic tendency slight injury may determine the localisation of the malady in a particular joint. At the recent meeting of the Royal Society of Medicine R. G. Gordon 4 emphasised the importance of trauma at the onset of cases of arthritis deformans, and it is common experience, too, that in the later stages of the disease, when patients become awkward and clumsy in their movements, a bad fall may follow a slight slip or trip, and fractures may result from a trifling cause. The formation of callus may be poor and union is sometimes much delayed. The association of accident with cases of arthritis deformans is of considerable importance when claims for compensation are likely to be made. E. Sonntag 5 lays down the following guiding principles for assessing these cases : (1) The accident must be well authenticated ; retrospective claims should be viewed with suspicion. (2) The accident must have involved the joint concerned ; if many joints are affected, an alleged accident probably had little to do with the disease. (3) The accident must be compatible with the injury, and sufficiently severe. The evidence is stronger when the claimant had to stop work and seek medical attention, and when there is injury to the skin and loss of blood. Effusion into a joint is not enough, since this often occurs in the course of the disease itself. (4) The time relationship must be considered, though here there is some latitude. The case is strengthened if the disease begins soon after the alleged accident. (5) A full investigation should be made for evidences of arthritis elsewhere. X ray examination is of special value, and should include comparisons with the corresponding joints of the opposite limb. Spondylitis is an important manifestation of arthritis deformans. It may be present to a gross extent without any disability; but symptoms may follow a slight injury, and often a severe hysteria is superadded. The statements of the patient and even of the witnesses must be thus sifted with care. Careful weighing of the evidence and a knowledge of the character and previous history of the claimant will usually enable a just decision to be made. It is in this type of case where medical experts may be approached by either side that a sharp conflict may result between 3 THE LANCET, 1926, ii., 1139. 4 THE LANCET, Feb. 23rd, 1929, p. 395. 5 Klin. Wochenschr., 1929 viii., 474.

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titrating sugar in urine and blood ; Mr. Victor Bonneycontributes a paper on the gynaecological aspect ofurology ; Mr. Duncan Morison gives an account ofexperimental work on routes of absorption in hydro-nephrosis, carried out with dyes in the totallyobstructed ureter ; Mr. R. Gordon Craig and Mr.R. K. Lee-Brown write on the pyelographic diagnosisof renal tumour, and Dr. Maurice Meltzer, of NewYork, on the surgical aspects of polycystic disease ofthe kidney, while Mr. H. Temple Mursell relates theafter-history of a case of nephrectomy for polycystickidney. Other features are notes on interestingcases; urological hints for practitioners, biochemicalnotes, a copious body of abstracts, and an indexmedicus. The size of the publication is quarto ; it is

printed on highly glazed paper and illustrated withmany excellent radiograms, photographs, and drawings.The coloured plate by Mr. Thornton Shiells, illustratinga hydronephrotic kidney with a suprarenal cyst insagittal section, is an admirable example of litho-graphic work.We wish our new contemporary many happy returns

of the day. ____

IMMUNITY TO CANCER.

WHEN a small piece of a tumour is inoculated into B Ian animal of the same species as that in which itoriginated spontaneously, the inoculated cells continue to grow and form a new tumour, the host supplying d

them with nourishment by means of the new blood-vessels of the stroma which it furnishes. It is possibleexperimentally to affect an animal in such a way thatthe inoculated tumour cells do not grow and do notform a new tumour. They remain alive for a few days xand are then absorbed ; they behave, in fact, just asnormal tissue transplanted from one animal to another Aof the same species. This condition has been described ias

"

immunity." It can be induced by injectinganimals, before the inoculation of tumour cells, withnormal tissues of the same species, and it is also ..

induced when a transplanted tumour is made toundergo regression-for instance, by means ofradium. When the phenomenon was first discovered25 years ago, it seemed to have possibilities of thera-peutic application. But exhaustive investigation byworkers of the Imperial Cancer Research Fund servedto disappoint these hopes. It was found that theblood of an " immune " animal had no toxic or lethalaction on the implanted cells. If an animal bearingan implanted tumour was rendered

" immune " bythe injection of normal tissues, so that a secondinoculation failed to take, the tumour inoculatedbefore " immunisation " was not checked in itsgrowth but continued to grow. Moreover, where amalignant new growth had developed spontaneously,injection of normal tissue failed to render the affectedanimal immune against the successful inoculation ofits own tumour, and a spontaneous development oftumours was observed in " immunised " animals.The conclusion was inevitable, therefore, that thecondition was not an immunity against cancerouscells, but rather an interference with the process bywhich the inoculated cells of one animal establishedthemselves in another animal of the same species. Itis not an "immunity to cancer " but an " immunity tothe transplantation of cancer."Work on this subject up to the year 1913 was

reviewed by Dr. W. H. Woglom, of the Crocker CancerResearch Fund of Columbia University, in his bookThe Study of Experimental Cancer,l and in the Marchnumber of the Cancer Review 2 he gives us an accountof the further investigations carried out between 1913and 1928. His paper is a truly monumental contribu-tion to scientific literature and has been prepared withthe thoroughness characteristic of its author. Thebibliography contains references to more than 600papers and a study of the text makes it clear that

1 The Study of Experimental Cancer. New York. 1913.2 Immunity to Transplanted Tumour. The Cancer Review,

March, 1929.

Dr. Woglom has read almost all of these in theoriginal. Nor is it a dry compilation of observationsand conclusions recorded in the literature, for it isseverely critical in tone. Of a number of conclusionswhich are reached the following may be quoted:" Immunity to transplantable tumours is a generalizedrefractory condition which appears to be entirelyunrelated to other forms of immunity... The outcome ofinoculation is determined by an interplay between thehostility of the host and the proliferative vigour of theimplant, hence an absolute immunity does not exist...Resistance is effective during the first few days followinginoculation, but entirely powerless against an estab-lished tumour. Nothing may accordingly be hopedfor at present in respect to a successful therapyfrom this direction."

There is, however, an entirely different immunityto cancer which has been disclosed by the recent workof Dr. J. A. Murray and his colleagues. This immunityis directed not against the successful inoculation ofcancerous cells but against the transformation ofnormal cells into cancerous cells. There are systemicfactors which determine the susceptibility of an

organism to the genesis of cancer. Some aspects ofthis problem were dealt with by Dr. Murray in theTwenty-fifth Annual Report of the Imperial CancerResearch Fund and their significance was discussedin our columns.3 It is obvious that if further pro-gress along these lines is possible it would be in thedirection of preventing cancer rather than curing it.

ARTHRITIS DEFORMANS AND ACCIDENTS.

IN persons of rheumatic tendency slight injurymay determine the localisation of the malady in aparticular joint. At the recent meeting of the RoyalSociety of Medicine R. G. Gordon 4 emphasised theimportance of trauma at the onset of cases of arthritisdeformans, and it is common experience, too, thatin the later stages of the disease, when patientsbecome awkward and clumsy in their movements, abad fall may follow a slight slip or trip, and fracturesmay result from a trifling cause. The formation ofcallus may be poor and union is sometimes muchdelayed. The association of accident with cases ofarthritis deformans is of considerable importancewhen claims for compensation are likely to be made.E. Sonntag 5 lays down the following guiding principlesfor assessing these cases : (1) The accident must bewell authenticated ; retrospective claims should beviewed with suspicion. (2) The accident must haveinvolved the joint concerned ; if many joints are

affected, an alleged accident probably had little todo with the disease. (3) The accident must becompatible with the injury, and sufficiently severe.The evidence is stronger when the claimant had tostop work and seek medical attention, and when thereis injury to the skin and loss of blood. Effusion intoa joint is not enough, since this often occurs in thecourse of the disease itself. (4) The time relationshipmust be considered, though here there is some latitude.The case is strengthened if the disease begins soonafter the alleged accident. (5) A full investigationshould be made for evidences of arthritis elsewhere.X ray examination is of special value, and shouldinclude comparisons with the corresponding jointsof the opposite limb. Spondylitis is an importantmanifestation of arthritis deformans. It may be

present to a gross extent without any disability;but symptoms may follow a slight injury, and oftena severe hysteria is superadded. The statementsof the patient and even of the witnesses must bethus sifted with care. Careful weighing of theevidence and a knowledge of the character andprevious history of the claimant will usually enablea just decision to be made. It is in this type ofcase where medical experts may be approached byeither side that a sharp conflict may result between

3 THE LANCET, 1926, ii., 1139.4 THE LANCET, Feb. 23rd, 1929, p. 395.

5 Klin. Wochenschr., 1929 viii., 474.

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the views of those called in. Such conflict oftenbrings medical evidence into disrepute in legalcircles, and could doubtless in large measure beavoided by the general acceptance of a few basic

principles such as those laid down by Dr. Sonntag.

THE PROGRESS OF CREMATION.

THE Cremation Society of England was foundedin 1874, and 11 years later, after the famous WelshDruid case, in which Mr. Justice Stephen held that itwas not an offence to burn a dead body, the firstcrematorium in this country was opened at Wokingfor public use. Since that time progress has neces-

’’

sarily been slow, but the 1928 report of the Societyshows that the number of cremations has beenincreasing more rapidly during the last few yearsthan formerly. In 1928 there were 3436 cremations,as compared with 3265 for the previous year, and thisrepresents nearly 30 per cent. increase on the previousfive years’ average. Twenty crematoria have nowbeen established in the British Islands, the two latestbeing at Bristol and Ipswich. The erection of onein Guernsey has been sanctioned by the StateCommittee, and it is anticipated that the buildingwill be opened for public use during the presentyear, whilst in Edinburgh also a crematorium is incourse of construction. The Council of the Societvnotes that the growth of cremation is comparativelyslow in many of the provincial centres, and it seemsobvious that the provision of a crematorium is notenough ; there must also be sustained local propa-ganda in its favour. During the year papers oncremation were read before a conference of theNational Association of Cemetery Superintendentsand at the Congress of the Royal Sanitary Instituteat Plymouth, and the Central Council of HealthEducation has permitted the Cremation Society toattend the numerous Health Week exhibitions held invarious parts of the country. Lectures to societiesand guilds have also been arranged, but from theeconomic point of view little immediate result canbe expected among the less wealthy classes of thecommunity. At the same time the spread of know-ledge to the masses may well enable some sort ofindustrial insurance scheme to be established in thefuture, so that cremation at death may be available toall who want it. In the meantime the Society iswell advised to go on advocating cremation from theaesthetic side rather than the standpoint of economicsand sanitation, for sentiment is probably the greatestobstacle to its universal adoption. Gardens of restor remembrance have become ordinary adjuncts to acrematorium and represent a compromise with thosewho look upon the cemetery as a desirable feature ofevery town or city, on almost the same footing as apublic park.One practical point about cremation should perhaps

be better known. If cremation is desired, it isnecessary to inform somebody of this fact beforehand,and the will is not a suitable document for conveyingthe information as often it is not opened until afterthe funeral. The practitioner should bear this inmind if he is called upon to give advice aboutcremation-advice which more and more people arelikely to ask of him.

__

AN OUTBREAK OF BRILL’S DISEASE IN ROME.

DURING the summer months, and more particularlyin August during the last few years, a febrile maladyhas made its appearance in Rome. The pyrexialasts 10-15 days, running a uniform course and isaccompanied by an exanthem of somewhat indefinitecharacter, and the disease is not contagious. A ’Ifavourable termination is the rule. Outbreaks haveoccurred from time to time since 1920, but in 1927and 1928 they became more numerous, 36 cases beingnotified in 1927 and 65 in 1928. The clinical picturecorresponds to that of Brill’s disease, which is heldto be an attenuated form of typhus fever. The I

illness begins with fever and headache ; the exanthem,which appears on the third or fourth day, takes theform of scarcely raised maculae of various size froma millet seed to a lentil, round, reddish in colour, andfrequently becoming petechial. The rash appearssimultaneously on the trunk and limbs and aftertwo days becomes diffuse over the abdomen and backand sometimes on the face. Among those attackedin 1927 and 1928 only three patients succumbed,two of them being of advanced age and suffering fromchronic vascular and cardiac lesions. In the onlycase where death seemed entirely due to the diseasehistological examination of the skin showed thechanges in the capillaries and the perivascularinfiltration characteristic of typhus fever. Personsof all ages and both sexes were attacked. Epidemio-logical investigation revealed the fact that 95 percent. of the patients lived in districts where a speciesof tick, Rhypicephalus, infected the dogs ; some ofthe patients asserted that they had found theseparasites on their bodies and exhibited cutaneouslesions strongly suggesting their presence. The closerelationship between the disease and typhus feverwas further indicated by the fact that the Weil-Felixreaction was positive in the majority of cases, atleast in adults, when the blood was tested at a latestage of the attack or during convalescence. Inchildren the Weil-Felix reaction was usually negative,possibly because in them the disease took a verymild form. Agglutination tests on patients affectedby the outbreaks showed that the thermostabilityof agglutinins could not be regarded as a reliablemethod of differentiation between typhus fever andBrill’s disease. The fact that in the Rome epidemicthe virus was an attenuated one is associated, accord-ing to G. Pecori, of the Department of PublicHealth,l with the nature of the insect carrier ofthe virus. The louse is excluded as a carrier inBrill’s disease, Marseilles fever, and the Romeepidemic. In the absence of lice, other insects mustbe implicated, and all the evidence seems to point tothe dog tick. These ticks, which have a summerdevelopment cycle, are believed to carry the virusfrom unknown habitats to healthy persons. Themodifications the virus undergoes during its passagethrough an intermediate host other than the lousemay account for the changed epidemiological charac-teristics of the outbreaks which are transformed intoa summer infection, sporadic, non-contagious, andrunning a mild clinical course. This attenuated formis called by Pecori " non-spreading summer dermo-typhus." The appearance of dermotyphus of Brill’stype in any locality does not in the least degreeconstitute an index of epidemic recrudescence oftrue exanthematous typhus.

CEREBRAL FORMS OF INFANTILE PARALYSIS.

ACUTE poliomyelitis may present itself clinicallyin many different ways but sooner or later as thedisease evolves most cases reveal themselves as dueto infection of certain parts of the spinal cord. Some-times the virus seems to attack the higher parts ofthe nervous system such as the brain-stem, whilstthe existence of frankly cerebral forms of the disease,leading, for example, to hemiplegia, was suspectedas long ago as 1885 by Pierre Marie. The cerebralvarieties, which may take the form of a pureencephalitis, often lead to difficulties in diagnosis,the physical signs depending very much on what partof the brain the virus attacks. Parkinsoniansymptoms have been reported by Marinesco andthe confusion of epidemic lethargic encephalitiswith polio-encephalitis is by no means uncommon3r surprising. Thus Mouriquand and co-workers 2have lately described the case of a boy, aged 4,who died after only five days’ illness which took the

1 Il Policlinico, Practical Section, Feb. 4th, p. 151.2 Mouriquand, G., Bernheim, M., and Dechaume, J. : Jour.

de Med. de Lyon, Feb. 20th, p. 105.