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THE EARLY OCCURRENCE OF NERVOUS LESIONS IN POLIOMYELITIS
CARDIOVASCULAR SYPHILIS
of the reasonable requirements of possible purchasers should be one of the considerations in granting licences. In spite of that intended limitation, hundreds of licences had been granted in urban areas, even in close to chemists’ shops. It is common knowthat in many cases of the criminal use of poison the substance has been obtained in the form of agricultural or horticultural preparations. Mr. Young was entitled to protest in 1930, and Mr. Wippell Gadd to-day, that the new law confirms and even extends the wide concession which non-qualified vendors have managed to obtain. Parliament has sanctioned the change but public opinion may succeed in keeping its operation within proper limits.
proximity
ledge
CARDIOVASCULAR SYPHILIS
developments in radiology have made it diagnose syphilis of the cardiovascular system more often and at an earlier stage than formerly ; by means of X rays it has become possible to recognise an early dilatation of the ascending aorta and arch, to which part of the system syphilitic lesions are largely confined. Dr. 0. Brenner1 reports a series of cases in which the findings, both before and after death, are closely comparable with those of other observers. Of 102 patients, 50 showed aortic incompetence, 28 aneurysm, 14 both these lesions, and 10 neither of them. As is the ordinary experience, the usual order of appearance of symptoms was dyspnoea, angina, congestive failure ; and in about 9 per cent. of cases physical signs were discovered accidentally when there were no symptoms referable to the circulatory system. Angina, commonly nocMODERN
possible
to
was recorded in 43 per cent., in more than half of which the aortic valve was incompetent. In a few of the cases of angina, however, aneurysm alone was found at autopsy, there being no evidence of aortic incompetence or coronary obstruction. Congestive failure is a late and grave manifestation. With it the normal rhythm of the heart is preserved, auricular fibrillation being remarkably rare in cardiovascular syphilis. Aortic incompetence was the lesion most often associated with congestive failure ; in other cases coronary orifice obstruction, coexisting coronary atheroma, and aneurysm were found. Some patients with failure showed neither coronary lesions nor aortic incompetence, and in these cases there was no clear evidence that hypertension was a factor. When congestion has made its appearance the outlook is extremely bad and survival for more than a few months unlikely. Treatment of the symptoms of cardiovascular syphilis does not differ from the treatment of the same symptoms arising from other forms of heart disease. Specific treatment designed to arrest the syphilitic process in the aorta and its valve should be cautiously used, and in the presence of angina or congestion, the intravenous arsenicals should not be given. Otherwise they may be used in small doses after an initial period of two or three months’ treatment with iodide, mercury, and bismuth. There is evidence that such remedies give relief from symptoms and increase the duration of life.
turnal,
HEALTH OF THE NAVY ONE HUNDRED YEARS AGO AN interesting article by Surgeon-Captain Pickering Pick, R.N., will be found in the last quarterly issue of the Journal of the Royal Naval Medical Service. The actual period selected by Surgeon-Captain Pick for comment is the six months from April to September, 1838, at which time the state of the medical depart1 Birmingham Med. Rev., Sept., 1933, p. 161.
1159
ment of the Navy was receiving conspicuous attention in THE LANCET and his article is inspired by Wakley’s characteristic freedom of speech. Surgeon-Captain Pick quotes statements showing that an invidious social distinction pursued naval medical officers in their career when they certainly deserved every support in their hard and ill-paid duties. When dealing with the high mortality in the Service and the conditions of rank, pay, and promotion existing among the medical officers, Wakley showed that in the list of assistant surgeons between the years 1827 and 1834 there was a loss amounting to nearly 5!per cent. annually from death or dismissal, while the promotions in the same years amounted to 4 per cent. The figures at the time they were published were substantiated from other returns, and apparently the death-rate of these officers was three times that of the ordinary population. The question emerged in Wakley’s words "what will a man give in exchange for his life, for 3s. 6d. a day, and the prospect of never being made a surgeon " The interests of naval medical officers 100 years ago were brought to the attention of the medical profession and to that of their seniors in the Service with remarkable force in our editorial articles, and correspondence to be found in the second volume of THE LANCET for 1837-38 makes striking reading ; but although conditions to-day are so profoundly altered there is, and there always will be, room for
improvement. THE EARLY OCCURRENCE OF NERVOUS LESIONS IN POLIOMYELITIS THE efficacy of convalescent or of pooled adult serum in the treatment of poliomyelitis is still a matter of controversy, and the burden of proof is on those who still believe that this method significantly lowers the frequency or severity of paralysis.1 The final verdict must be given on empirical trial, but our views as to how far that trial should extend will clearly be influenced by any ancillary evidence that may become available. A finding that has an obvious bearing on the main issue has recently been recorded by Kramer and Parker.2These workers, having available a strain of poliomyelitis virus that was known to be infective when administered by the nasopharyngeal route, inoculated six Macacus rhesus monkeys intranasally on each of three successive days with a suspension of virus-containing cord. The animals were kept under careful and continuous observation, temperatures being taken twice daily. One monkey was killed on the day following the third injection of virus, and one on each day thereafter until all six had been killed. Sections of the brain and cord were cut and examined in every case. The first two animals killed had shown no signs of illness and no rise in temperature, but the brain and cord showed definite signs of involvement, including oedema of the pia, cedema and congestion of the cord, infiltration of the grey matter, areas of haemorrhage, and occasional chromatolysis and neuronophagia of the ganglion cells. The monkey killed on the third day after the last intranasal injection showed no signs of illness, but had a raised temperature for The involvement of some hours before it was killed. the brain and cord revealed by histological examination was of the same kind as that found in the other cases, but more advanced. The monkey killed on the fourth day had had a raised temperature for 24 hours, and showed a mild tremor that became evident only on extreme exertion. The fifth and sixth monkeys showed the typical paralytic symptoms. See THE LANCET, 1932, ii., 1063: 1933, i., 1352 ; 1933, ii., 420. 2 Proc. Soc. Exp. Biol. and Med., 1933, xxx., 1417.
1160
SCIENTIFIC STUDIES AT CAMBRIDGE
The central nervous system of each of these last three monkeys showed the characteristic changes of
poliomyelitis. As the authors point out, the presence of definite lesions so soon after the intranasal administration of virus, and 48 hours or more before any clinical manifestation of illness, suggests that convalescent serum given after such symptoms have appeared, but before paralysis has supervened, is unlikely to have any very significant protective effect. If these findings are confirmed by subsequent workers they will clearly have to be regarded as adverse to the case for convalescent-serum therapy. nervous
SCIENTIFIC STUDIES AT CAMBRIDGE
A REPORT of progress in the Cambridge academic year ending September, 1933, has been issued in connexion with the Rockefeller scheme for the building of the new University library and for the promotion of the study of the physical and biological sciences. From the combined resources of the Rockefeller endowment fund and the Plummer Fund large grants were made during the year towards the endowments, but the University has still to collect over 50,000 for the advancement of the scheme for physical and biological sciences ; in response to the collection of this sum by the University, 105,000 will be received from the International Education Board. A special feature of the report is the note on the scheme for the new zoological laboratory, the building for which is rising rapidly, though it is probable that it will not be complete for another year. Old graduates in medicine will realise the site of the building from the description given in the report, and may be a little surprised to see that the name of the great Humphry should be misspelt in a document emanating from the Cambridge University Association. RADIODERMATITIS AND CANCER
CLINICAL observation of the development of cancer of the skin among radiologists has prompted Dr. Antoine B6cl6re1 to discuss the genesis of this condition in relation to the cancer problem as a whole. Before seeking to discover the essential cause of cancer we may ask ourselves, he says, whether it should be included among the pathological affections of external or internal origin. It is generally accepted at the present time that the various mechanical, chemical, and physical agents, and the parasites which cause cancer, do so by acting as chronic irritants setting up a chronic inflammation. As the multiplicity and diversity of these agents precludes specificity of action, further analysis of the problemaccording to Beclere-depends upon the answer to the question whether alterations which result from their action stir up properties originally inherent in the injured cells or whether the condition which has been brought about favours the intervention of yet another unknown factor. According to the first hypothesis the development of cancer is the ultimate link in a long chain of uninterrupted events beginning with inflammation and going on to progressive hyperplasia. But in Beclere’s view clinical study of radiologist’s cancer does not lend support to continuity in the development of the process. He sees the onset of malignant change as a strange accidental event superimposed on various non-specific lesions as though suddenly a new factor had been added to the already injured skin. His reasons are first that this form of cancer occurs in only a small minority of very 1
Bull. de l’Acad. de Méd., 1933, cx., 156.
people whose skin has been affected. is no parallelism between the severity there Secondly, of the cutaneous lesions and the appearance or absence of cancer. Finally, close examination of the actual skin lesion in no way supports a theory of chronic irritation followed by inflammation nor a gradual progressive hyperplasia ending in malignancy. The affected skin is in fact atrophic. It is silky or glossy and thin ; has lost hair follicles, sebaceous and sweat glands. The general effect is of a devitalised rather than a stimulated or irritated organ provided, of course, that no complicating injury or infection is present. Radiodermatitis is in fact not an essential part of the process. When cancer develops it starts many months, or years even, after exposure, as a small circumscribed ulcer or warty excrescence at one particular spot in a relatively vast expanse of atrophic skin, every part of which appears on microscopic examination as well as to the naked eye to be identical. What is it that determines this localised origin, or predilection as it were, of malignant change for any one particular spot ? Béclère postulates an additional factor of external origin-whose action is favoured by pre-existing changes. What he has once more stated is that cancer has a focal origin. Tarred mice demonstrate the same fact. Warts develop from single or multiple points of origin in a large expanse of apparently identical atrophic skin. This is one of the knotty points and stumbling-blocks of most cancer theories. In experimental skin tumours of mice and men it is not unreasonable to call in some additional external factor to account for this focal origin, but as an explanation of the focal origin of internal, spontaneously occurring, tumours it is less numerous
satisfactory. PROPRIETARY HOSPITALS IN the United States of America there are about 7000 hospitals with 1,000,000 beds representing a capital expenditure on land, buildings, and equipment of over 625,000,000. Apparently about 27 per cent. of the hospitals, including some of the largest, are owned by the central or local government’ authorities ; they provide accommodation for persons whose segregation is desirable in the public interest-
of communicable disease, including tuberculosis, and of mental disease-and also for soldiers, sailors, war veterans, and the destitute. With few exceptions these institutions do not receive paying patients. Nearly 40 per cent. of the remainder are non-profit, or charitable institutions, although most of them have a large proportion of paying patients; in many the fees paid amount to at least half the current expenses. Besides these there are about 2440 proprietary hospitals organised on a business basis, the profits, if any, accruing to the persons providing the capital invested. The majority of these proprietary hospitals, which are to be found chiefly in the smaller towns of the southern and western States, are owned by individuals or partnerships, but nearly 600 belong to companies formed for the purpose of providing a hospital. The proprietary hospital is usually small (the average number of beds is not more than 30), and provides general medical and surgical care ; a few limit themselves to some special kind of treatment. Not infrequently it is owned and managed by a medical practitioner, and in a considerable number of cases it forms an annexe to the practitioner’s consulting-room or " office." It is intended for patients who can afford to pay the cost of hospital services, and is used mainly for cases of acute illness. Non-paying patients are not admitted, but free first-aid treatment is given cases
of the reasonable requirements of possible purchasers should be one of the considerations in granting licences. In spite of that intended limitation, hundreds of licences had been granted in urban areas, even in close to chemists’ shops. It is common knowthat in many cases of the criminal use of poison the substance has been obtained in the form of agricultural or horticultural preparations. Mr. Young was entitled to protest in 1930, and Mr. Wippell Gadd to-day, that the new law confirms and even extends the wide concession which non-qualified vendors have managed to obtain. Parliament has sanctioned the change but public opinion may succeed in keeping its operation within proper limits.
proximity
ledge
CARDIOVASCULAR SYPHILIS
developments in radiology have made it diagnose syphilis of the cardiovascular system more often and at an earlier stage than formerly ; by means of X rays it has become possible to recognise an early dilatation of the ascending aorta and arch, to which part of the system syphilitic lesions are largely confined. Dr. 0. Brenner1 reports a series of cases in which the findings, both before and after death, are closely comparable with those of other observers. Of 102 patients, 50 showed aortic incompetence, 28 aneurysm, 14 both these lesions, and 10 neither of them. As is the ordinary experience, the usual order of appearance of symptoms was dyspnoea, angina, congestive failure ; and in about 9 per cent. of cases physical signs were discovered accidentally when there were no symptoms referable to the circulatory system. Angina, commonly nocMODERN
possible
to
was recorded in 43 per cent., in more than half of which the aortic valve was incompetent. In a few of the cases of angina, however, aneurysm alone was found at autopsy, there being no evidence of aortic incompetence or coronary obstruction. Congestive failure is a late and grave manifestation. With it the normal rhythm of the heart is preserved, auricular fibrillation being remarkably rare in cardiovascular syphilis. Aortic incompetence was the lesion most often associated with congestive failure ; in other cases coronary orifice obstruction, coexisting coronary atheroma, and aneurysm were found. Some patients with failure showed neither coronary lesions nor aortic incompetence, and in these cases there was no clear evidence that hypertension was a factor. When congestion has made its appearance the outlook is extremely bad and survival for more than a few months unlikely. Treatment of the symptoms of cardiovascular syphilis does not differ from the treatment of the same symptoms arising from other forms of heart disease. Specific treatment designed to arrest the syphilitic process in the aorta and its valve should be cautiously used, and in the presence of angina or congestion, the intravenous arsenicals should not be given. Otherwise they may be used in small doses after an initial period of two or three months’ treatment with iodide, mercury, and bismuth. There is evidence that such remedies give relief from symptoms and increase the duration of life.
turnal,
HEALTH OF THE NAVY ONE HUNDRED YEARS AGO AN interesting article by Surgeon-Captain Pickering Pick, R.N., will be found in the last quarterly issue of the Journal of the Royal Naval Medical Service. The actual period selected by Surgeon-Captain Pick for comment is the six months from April to September, 1838, at which time the state of the medical depart1 Birmingham Med. Rev., Sept., 1933, p. 161.
1159
ment of the Navy was receiving conspicuous attention in THE LANCET and his article is inspired by Wakley’s characteristic freedom of speech. Surgeon-Captain Pick quotes statements showing that an invidious social distinction pursued naval medical officers in their career when they certainly deserved every support in their hard and ill-paid duties. When dealing with the high mortality in the Service and the conditions of rank, pay, and promotion existing among the medical officers, Wakley showed that in the list of assistant surgeons between the years 1827 and 1834 there was a loss amounting to nearly 5!per cent. annually from death or dismissal, while the promotions in the same years amounted to 4 per cent. The figures at the time they were published were substantiated from other returns, and apparently the death-rate of these officers was three times that of the ordinary population. The question emerged in Wakley’s words "what will a man give in exchange for his life, for 3s. 6d. a day, and the prospect of never being made a surgeon " The interests of naval medical officers 100 years ago were brought to the attention of the medical profession and to that of their seniors in the Service with remarkable force in our editorial articles, and correspondence to be found in the second volume of THE LANCET for 1837-38 makes striking reading ; but although conditions to-day are so profoundly altered there is, and there always will be, room for
improvement. THE EARLY OCCURRENCE OF NERVOUS LESIONS IN POLIOMYELITIS THE efficacy of convalescent or of pooled adult serum in the treatment of poliomyelitis is still a matter of controversy, and the burden of proof is on those who still believe that this method significantly lowers the frequency or severity of paralysis.1 The final verdict must be given on empirical trial, but our views as to how far that trial should extend will clearly be influenced by any ancillary evidence that may become available. A finding that has an obvious bearing on the main issue has recently been recorded by Kramer and Parker.2These workers, having available a strain of poliomyelitis virus that was known to be infective when administered by the nasopharyngeal route, inoculated six Macacus rhesus monkeys intranasally on each of three successive days with a suspension of virus-containing cord. The animals were kept under careful and continuous observation, temperatures being taken twice daily. One monkey was killed on the day following the third injection of virus, and one on each day thereafter until all six had been killed. Sections of the brain and cord were cut and examined in every case. The first two animals killed had shown no signs of illness and no rise in temperature, but the brain and cord showed definite signs of involvement, including oedema of the pia, cedema and congestion of the cord, infiltration of the grey matter, areas of haemorrhage, and occasional chromatolysis and neuronophagia of the ganglion cells. The monkey killed on the third day after the last intranasal injection showed no signs of illness, but had a raised temperature for The involvement of some hours before it was killed. the brain and cord revealed by histological examination was of the same kind as that found in the other cases, but more advanced. The monkey killed on the fourth day had had a raised temperature for 24 hours, and showed a mild tremor that became evident only on extreme exertion. The fifth and sixth monkeys showed the typical paralytic symptoms. See THE LANCET, 1932, ii., 1063: 1933, i., 1352 ; 1933, ii., 420. 2 Proc. Soc. Exp. Biol. and Med., 1933, xxx., 1417.
1160
SCIENTIFIC STUDIES AT CAMBRIDGE
The central nervous system of each of these last three monkeys showed the characteristic changes of
poliomyelitis. As the authors point out, the presence of definite lesions so soon after the intranasal administration of virus, and 48 hours or more before any clinical manifestation of illness, suggests that convalescent serum given after such symptoms have appeared, but before paralysis has supervened, is unlikely to have any very significant protective effect. If these findings are confirmed by subsequent workers they will clearly have to be regarded as adverse to the case for convalescent-serum therapy. nervous
SCIENTIFIC STUDIES AT CAMBRIDGE
A REPORT of progress in the Cambridge academic year ending September, 1933, has been issued in connexion with the Rockefeller scheme for the building of the new University library and for the promotion of the study of the physical and biological sciences. From the combined resources of the Rockefeller endowment fund and the Plummer Fund large grants were made during the year towards the endowments, but the University has still to collect over 50,000 for the advancement of the scheme for physical and biological sciences ; in response to the collection of this sum by the University, 105,000 will be received from the International Education Board. A special feature of the report is the note on the scheme for the new zoological laboratory, the building for which is rising rapidly, though it is probable that it will not be complete for another year. Old graduates in medicine will realise the site of the building from the description given in the report, and may be a little surprised to see that the name of the great Humphry should be misspelt in a document emanating from the Cambridge University Association. RADIODERMATITIS AND CANCER
CLINICAL observation of the development of cancer of the skin among radiologists has prompted Dr. Antoine B6cl6re1 to discuss the genesis of this condition in relation to the cancer problem as a whole. Before seeking to discover the essential cause of cancer we may ask ourselves, he says, whether it should be included among the pathological affections of external or internal origin. It is generally accepted at the present time that the various mechanical, chemical, and physical agents, and the parasites which cause cancer, do so by acting as chronic irritants setting up a chronic inflammation. As the multiplicity and diversity of these agents precludes specificity of action, further analysis of the problemaccording to Beclere-depends upon the answer to the question whether alterations which result from their action stir up properties originally inherent in the injured cells or whether the condition which has been brought about favours the intervention of yet another unknown factor. According to the first hypothesis the development of cancer is the ultimate link in a long chain of uninterrupted events beginning with inflammation and going on to progressive hyperplasia. But in Beclere’s view clinical study of radiologist’s cancer does not lend support to continuity in the development of the process. He sees the onset of malignant change as a strange accidental event superimposed on various non-specific lesions as though suddenly a new factor had been added to the already injured skin. His reasons are first that this form of cancer occurs in only a small minority of very 1
Bull. de l’Acad. de Méd., 1933, cx., 156.
people whose skin has been affected. is no parallelism between the severity there Secondly, of the cutaneous lesions and the appearance or absence of cancer. Finally, close examination of the actual skin lesion in no way supports a theory of chronic irritation followed by inflammation nor a gradual progressive hyperplasia ending in malignancy. The affected skin is in fact atrophic. It is silky or glossy and thin ; has lost hair follicles, sebaceous and sweat glands. The general effect is of a devitalised rather than a stimulated or irritated organ provided, of course, that no complicating injury or infection is present. Radiodermatitis is in fact not an essential part of the process. When cancer develops it starts many months, or years even, after exposure, as a small circumscribed ulcer or warty excrescence at one particular spot in a relatively vast expanse of atrophic skin, every part of which appears on microscopic examination as well as to the naked eye to be identical. What is it that determines this localised origin, or predilection as it were, of malignant change for any one particular spot ? Béclère postulates an additional factor of external origin-whose action is favoured by pre-existing changes. What he has once more stated is that cancer has a focal origin. Tarred mice demonstrate the same fact. Warts develop from single or multiple points of origin in a large expanse of apparently identical atrophic skin. This is one of the knotty points and stumbling-blocks of most cancer theories. In experimental skin tumours of mice and men it is not unreasonable to call in some additional external factor to account for this focal origin, but as an explanation of the focal origin of internal, spontaneously occurring, tumours it is less numerous
satisfactory. PROPRIETARY HOSPITALS IN the United States of America there are about 7000 hospitals with 1,000,000 beds representing a capital expenditure on land, buildings, and equipment of over 625,000,000. Apparently about 27 per cent. of the hospitals, including some of the largest, are owned by the central or local government’ authorities ; they provide accommodation for persons whose segregation is desirable in the public interest-
of communicable disease, including tuberculosis, and of mental disease-and also for soldiers, sailors, war veterans, and the destitute. With few exceptions these institutions do not receive paying patients. Nearly 40 per cent. of the remainder are non-profit, or charitable institutions, although most of them have a large proportion of paying patients; in many the fees paid amount to at least half the current expenses. Besides these there are about 2440 proprietary hospitals organised on a business basis, the profits, if any, accruing to the persons providing the capital invested. The majority of these proprietary hospitals, which are to be found chiefly in the smaller towns of the southern and western States, are owned by individuals or partnerships, but nearly 600 belong to companies formed for the purpose of providing a hospital. The proprietary hospital is usually small (the average number of beds is not more than 30), and provides general medical and surgical care ; a few limit themselves to some special kind of treatment. Not infrequently it is owned and managed by a medical practitioner, and in a considerable number of cases it forms an annexe to the practitioner’s consulting-room or " office." It is intended for patients who can afford to pay the cost of hospital services, and is used mainly for cases of acute illness. Non-paying patients are not admitted, but free first-aid treatment is given cases