- Email: [email protected]
TRANQUILLISERS AND SOCIETY
775
serious injury by their method was slight, but admitted that any break in the rectal or colonic mucosa might lead to ischiorectal abscess or perforation of the bowel. At some hospitals, including St. Mark’s, rectal biopsy has been adopted, almost as a routine, to confirm a diagnosis of carcinoma and as an aid to the diagnosis of obscure lesions ; and it has been found that material can be safely taken in the outpatient department without anaesthesia and without any preliminary preparation, provided that suitable instruments are used and that the operator is experienced in sigmoidoscopic
technique.
Annotations ORAL PREPARATIONS FOR TREATMENT OF PERNICIOUS ANÆMIA IF our present ideas about the aetiology of pernicious anaemia, are correct, it should be possible to treat patients successfully by giving them orally a preparation of intrinsic factor (hæmopoietin) together with a relatively small dose-say 30-45 µg.—of vitamin B12. Preparations of vitamin B12 and intrinsic factor made from hog’s pylorus or hog’s duodenum have been marketed ; but the results have been curiously disappointing. Blackburn et al.1 used a preparation dispensed in tablets each of which contained 6 µg. of vitamin Bl2 and 30 mg. of an intrinsic-factor concentrate. They gave five tablets a day to 5 patients with pernicious anaemia in relapse ; 4 responded reasonably, if slowly, but the 5th did not respond at all, though 30 µg. of vitamin B12 given intramuscularly each day produced a satisfactory rise in red cells and haemoglobin. Maintenance with one tablet a day showed that after a time, usually about six months, the blood-levels began to fall, and in 1 patient signs of neurological involvement developed. Blackburn et al. concluded that either they had not given big enough doses or the effectiveness of the intrinsic-factor concenDr. Schwartz, Dr. Lous, and trate was falling off. Professor Meulengracht in Copenhagen have met with similar disappointing results, and on p. 751 of this issue report investigations that suggest another explanation. They used the test devised by R. F. Schilling that utilises the urinary excretion of an orally administered test-dose of vitamin B12 labelled with radioactive cobalt. In a healthy person vitamin B12 is absorbed in the intestine and excreted in the urine, and the amount excreted gives a measure of the degree of intestinal absorption. The patient with untreated pernicious ansemia absorbs hardly any vitamin BI2’ so very little appears in the urine ; but if an effective source of intrinsic factor is given with the vitamin B12, absorption takes place and is reflected in the urinary excretion. In health 10-38% of the orally administered vitamin Bl2 is excreted in the urine, whereas in untreated pernicious anaemia the figure is 0-8%. The Copenhagen workers gave a combination of labelled vitamin B12 and intrinsic factor made from hog’s pyloric mucosa to three groups of patients : those with untreated pernicious anaemia, those whose pernicious anaemia had been treated with intramuscular vitamin B12 or liver extract, and those whose anaemia had been treated orally with a combination of vitamin Bi2 and hog’s pyloric mucosa for periods ranging from six months to four years. They found, as have others,2 that up to a certain maximum the absorption of vitamin Buj increases with the amount of intrinsic factor given ; with their preparation, the most effective dose was about 100 mg. daily. When this dose of intrinsic factor, together 1. Blackburn, E. K., Cohen, H., Wilson, G. M. Brit. med. J. 1955, ii, 461. 2. Baker, S. J., Mollin, D. L. Brit. J. Hœmatol. 1955, 1, 46.
with labelled vitamin B12 was given to patients with untreated pernicious anaemia the greatest proportion of the test dose excreted in the urine was 20-25% ;patients whose pernicious anaemia had been treated with intramuscular vitamin B12 or liver gave a similar figure ; but most of the patients treated orally showed remarkably low urinary excretion figures, varying from nil to 16%. When a human source of intrinsic factor, in the form of 100 ml. of normal gastric juice, was given with the labelled vitamin B12, this was absorbed as fully by the third group of patients as by the other two groups. Dr. Schwartz and his colleagues consider that long treatment with heterologous intrinsic factor must be connected with the long-term failure of these orally administered combinations of vitamin B12 and intrinsic factor, but they cannot suggest an explanation. Wijrnenga,3 addressing the 1956 Hamburg conference on vitamin Bn and intrinsic factor, pointed out that there was evidence that intrinsic factor might be specific for each species, though it is known that activity is not limited to one species-for hog’s intrinsic factor is active in man. But he also cited some investigations suggesting that intrinsic-factor concentrates prepared from one species might contain substances that inhibit the absorption of vitamin B12 in other species. Williams et al.4 actually prepared intrinsic-factor fractions some of which augmented and some inhibited the absorption of vitamin B12’ judged by the Schilling test. Nevertheless physicians have had entirely satisfactory results from the treatment of pernicious anaemia over periods of many years by administration of relatively crude preparations of hog’s stomach. Thus Wilkinson 5 reported that of 441 patients treated for six or more years with preparations of desiccated hog’s stomach, only 15 relapsed ; these relapses occurred only because the patients neglected treatment and they responded promptly when given proper treatment again. The cause of the failure of the present intrinsic-factor concentrates may well lie in the method of preparation, and this needs to be fully explored as well as possible resistance, or inhibitors, arising because of the heterologous source of intrinsic factor. Meanwhile practitioners can take the hint and avoid these relatively very expensive oral preparations for the treatment of pernicious anaemia.
TRANQUILLISERS
AND SOCIETY abuse of tranquillisers has
CONCERN at the increasing been expressed by the W.H.O. Committee on Addictionproducing Drugs.6 In the U.S.A. in the first ten months of last year some 30,000 million tablets of one particular tranquillising drug are said to have been sold to the who public.- This figure is cited by Dickel and Dixon,7 " arising report 328 instances of " physical dangers from the treatment with tranquillisers of 8200 patients in the past eight years. The main thesis of Dickel and Dixon is that the dangers of abuse are altogether more subtle and pervasive than the occasional development of a skin rash or a blood dyscrasia. 8 They consider that such abuse has caused emotional, moral, and philosophical dangers to the patient ; dangers to medicine and the physician ; and dangers to the whole structure of society. In their experience, undesired emotional responses to tranquillising drugs occurred in 827 emotionally ill patients, whose condition was aggravated and distorted by these drugs. Equally disturbing were 1700 instances in which serious problems were created in the minds of essentially normal people by the misuse of tranquillisers. What very often 3. 4.
Wijmenga, H. G. In Vitamin B12 and Intrinsic Factor. Edited by H. C. Heinrich. Stuttgart, 1957; p. 156. Williams, W. L., Chow, B. F., Ellenbogen, L., Okuda, K. Ibid,
p. 250. 5. Wilkinson, J. F. Lancet, 1949, i, 291. 6. Tech. Rep. Wld Hlth Org. no. 116. 7. Dickel, H. A., Dixon, H. H. J. Amer. med. Ass. 8. See Lancet, Feb. 9, 1957, p. 308.
1957, 163,
422.
776
happened
was that a normal man went to his doctor for advice about a mildly distressing problem that had produced tension, worry, and anxiety. In place of advice and reassurance, the physician gave the latest tranquilliser. Commonly the drug produced not tranquillity but depression or other unwanted emotional reaction. The physician interpreted the new symptom as evidence of deep-seated mental illness, and the perplexed but essentially normal patient found himself classified as a serious mental case. Danger to the professional standards of medicine comes, Dickel and Dixon think, from the increasing tendency of doctors to prescribe, rather than to listen and diagnose, when confronted by a restless public, a growing pharmaceutical industry, an able advertising profession, and many truly anxious patients." Psychotherapy, they say, does not consist in writing prescriptions for tranquillisers, any more than the internist’s skill consists in prescribing the latest antibiotic. But the most insidious danger of all, according to Dickel and Dixon, is the sickness of a society which ranks the attainment of tranquillity, the freedom from anxiety, as its central aim. Throughout history " tension, alertness, alarmedness, fear, worry, anxiety and apprehension have been, are, and always will be important elements in the shaping of progress." But the new philosophy tells us that fear and anxiety are evidence of illness and require medical treatment with the latest soothing drug. "
ARTIFICIAL
PNEUMOTHORAX SxrrCE the temporary success of Cayley1 in 1885 and the permanent success of Forlanini2 in 1894, artificial pneumothorax (A.P.) has given many good results in pulmonary tuberculosis ; but severe complications have been commonenough to raise serious doubts about the true value of the method. In 1947 Rafferty 3 declared that the improperly used A.P. was more dangerous and lethal than thoracoplasty, the only difference being that the damage took longer to appear. There has always been a feeling that a balance must be struck between profit and loss-but that the loss was mainly due to mismanagement of the A.P. and could therefore be avoided. On the one hand, there were the hazards of too early induction in acute lesions ; on the other, there were risks in leaving it too late so that fibrosis and emphysema introduced other dangers. When longer bed rest and preliminary phrenic crush, with or without pneumoperitoneum, were used to counter the more serious consequences, results improved ; but effusion and atelectasis still ensued in some patients. Uncertainty remained, and the accumulating evidence about disappointing late results of A.P. did little to restore confidence. Nevertheless, an A.P. still had its attractions : it was easy to start and required little apparatus ; it avoided a major operation ; the patient’s assent, as a rule, was readily obtained ; and it had the merit of keeping the patient constantly under medical supervision, though often at the expense of lost working-time. Yet even before the advent of chemotherapy, the popularity of the A.P. was on the wane. Simmonds et al.4 recorded a decline in the number of A.p.s induced at Clare Hall Hospital from 1943 onwards; and chemotherapy, which might have been expected to restore the prestige of the A.p., in the event has not done Fewer inductions than ever are now perforrned and so. many physicians seem to be abandoning the method completely-as a result of personal experience and discussion with colleagues rather than because of published long-term results, which have always been hard to get. 1. 2. 3. 4.
London, Cayley, W. Middlesex Hospital Cayley Case Papers. 1885 ; vol. I, p. 50. Forlanini, C. Gazz. med. Ital., Torino, 1894, 45, 381. Rafferty, T. M. Artificial Pneumothorax in Pulmonary Tubereulosis. London, 1947. Simmonds, F. A. H., Laird, R., Macdonald, N. ii, 347.
Lancet, 1952,
In 1860 Walshe5 declared that there was " no warranty for the fanciful proposal to treat phthisis by producing artificial pnemnothorax " ; and many people would now agree with him. Chemotherapy can limit the complications of the A.P.,6—8 particularly pleural effusion; and Dixon9 has lately shown that the reduction is related to the duration of chemotherapy before induction. He thinks this development is an important advance in the history of pneumothorax, and so it is ; but the question many people will ask is how much does it matter ? The treat. ment of tuberculosis has changed fundamentally and it is now far from easy to justify the continued use of pneumo. thorax-a method which may conceivably reduce the Two years ago 10 we effectiveness of chemotherapy. the that the fate of A.P. would probably be suggested settled, not by a definitive controlled trial, but by the slow evolution of medical opinion ; and though at that time we had misgivings about letting the treatment drop into disuse without good reason, we cannot deny that opinion has further hardened against it. One of the few good words that are heard nowadays about the A.P. is that it is suitable for poorly developed countries where surgical conditions are primitive ; but this idea is dangerous, for the complications of A.P. often need major In such circumstances a surgery to overcome them. long period of continuous chemotherapy is safer, and probably more effective, without an A.P. ANTIGEN-ANTIBODY RESPONSES IN MULTIPLE SCLEROSIS FAMILIAR though we now are with the acute manifestations of allergic encephalomyelitis in laboratory animals, those most competent to judge have been reluctant to that a similar mechanism is implicated in assume multiple sclerosis. The clinical course of this condition, with its characteristic remissions, is one important reason for distinguishing it from the acute experimental disease. It is therefore of interest that in guineapigs and rabbits Bogdanove and Clark 11 have found that a further insult to the brain, delivered during the period of recovery from allergic encephalomyelitis, can induce histological changes of the same character at the site of damage. Such observations, if confirmed and extended, could bridge the gap by demonstrating that the acute disease confers on the central nervous system a form of tissue sensitivity which makes it vulnerable to further attacks. Another slant is suggested by a preliminary report from Honor Smith and her colleagues 12 on studies at Oxford which show that, on intrathecal injection of tuberculin, sensitised (Mantoux-positive) patients with multiple sclerosis react differently from other patients with the disease. About two years ago the investigators selected a group of 35 volunteers, all with multiple sclerosis of long standing, most of whom had been disabled for months or years. These were arranged in four groups according to their degree of sensitivity to the Mantoux test, and graded doses of purified protein derivative (r.p.D.) of tuberculin were given by the lumbar route. (A. control group of psychotic patients, in whom the meninges were otherwise normal, was used for comparison.) In patients with multiple sclerosis in whom the Mantoux test was negative the response to P.P.D. followed the normal pattern ; but in the Mantouxpositive groups the character of the reaction was clearly 5.
6. 7. 8. 9. 10. 11. 12.
Walshe,
W. H.
A Practical Treatise
on
the Diseases of the
Lungs. London, 1860 ; p. 314. Quoted by Marmion, T. Tubercle, 1957, 38, 63. H. B. 288. Tubercle, 1952, 33, Wright, Birath, G. Dis. Chest, 1953, 24, 245. Scadding, J. G. Lancet, 1955, ii, 154. Dixon, W. M. Tubercle, 1957, 38, 21. See loading article, Lancet, 1955, ii, 26. Bogdanove, L. H., Clark, G. J. Neuropath. 1957, 16, 57. Smith, H. V., Espir, M. L. E., Whitty, C. W. M., Russell, W. R. J. Neurol. Psychiat. 1957, 20, 1.
serious injury by their method was slight, but admitted that any break in the rectal or colonic mucosa might lead to ischiorectal abscess or perforation of the bowel. At some hospitals, including St. Mark’s, rectal biopsy has been adopted, almost as a routine, to confirm a diagnosis of carcinoma and as an aid to the diagnosis of obscure lesions ; and it has been found that material can be safely taken in the outpatient department without anaesthesia and without any preliminary preparation, provided that suitable instruments are used and that the operator is experienced in sigmoidoscopic
technique.
Annotations ORAL PREPARATIONS FOR TREATMENT OF PERNICIOUS ANÆMIA IF our present ideas about the aetiology of pernicious anaemia, are correct, it should be possible to treat patients successfully by giving them orally a preparation of intrinsic factor (hæmopoietin) together with a relatively small dose-say 30-45 µg.—of vitamin B12. Preparations of vitamin B12 and intrinsic factor made from hog’s pylorus or hog’s duodenum have been marketed ; but the results have been curiously disappointing. Blackburn et al.1 used a preparation dispensed in tablets each of which contained 6 µg. of vitamin Bl2 and 30 mg. of an intrinsic-factor concentrate. They gave five tablets a day to 5 patients with pernicious anaemia in relapse ; 4 responded reasonably, if slowly, but the 5th did not respond at all, though 30 µg. of vitamin B12 given intramuscularly each day produced a satisfactory rise in red cells and haemoglobin. Maintenance with one tablet a day showed that after a time, usually about six months, the blood-levels began to fall, and in 1 patient signs of neurological involvement developed. Blackburn et al. concluded that either they had not given big enough doses or the effectiveness of the intrinsic-factor concenDr. Schwartz, Dr. Lous, and trate was falling off. Professor Meulengracht in Copenhagen have met with similar disappointing results, and on p. 751 of this issue report investigations that suggest another explanation. They used the test devised by R. F. Schilling that utilises the urinary excretion of an orally administered test-dose of vitamin B12 labelled with radioactive cobalt. In a healthy person vitamin B12 is absorbed in the intestine and excreted in the urine, and the amount excreted gives a measure of the degree of intestinal absorption. The patient with untreated pernicious ansemia absorbs hardly any vitamin BI2’ so very little appears in the urine ; but if an effective source of intrinsic factor is given with the vitamin B12, absorption takes place and is reflected in the urinary excretion. In health 10-38% of the orally administered vitamin Bl2 is excreted in the urine, whereas in untreated pernicious anaemia the figure is 0-8%. The Copenhagen workers gave a combination of labelled vitamin B12 and intrinsic factor made from hog’s pyloric mucosa to three groups of patients : those with untreated pernicious anaemia, those whose pernicious anaemia had been treated with intramuscular vitamin B12 or liver extract, and those whose anaemia had been treated orally with a combination of vitamin Bi2 and hog’s pyloric mucosa for periods ranging from six months to four years. They found, as have others,2 that up to a certain maximum the absorption of vitamin Buj increases with the amount of intrinsic factor given ; with their preparation, the most effective dose was about 100 mg. daily. When this dose of intrinsic factor, together 1. Blackburn, E. K., Cohen, H., Wilson, G. M. Brit. med. J. 1955, ii, 461. 2. Baker, S. J., Mollin, D. L. Brit. J. Hœmatol. 1955, 1, 46.
with labelled vitamin B12 was given to patients with untreated pernicious anaemia the greatest proportion of the test dose excreted in the urine was 20-25% ;patients whose pernicious anaemia had been treated with intramuscular vitamin B12 or liver gave a similar figure ; but most of the patients treated orally showed remarkably low urinary excretion figures, varying from nil to 16%. When a human source of intrinsic factor, in the form of 100 ml. of normal gastric juice, was given with the labelled vitamin B12, this was absorbed as fully by the third group of patients as by the other two groups. Dr. Schwartz and his colleagues consider that long treatment with heterologous intrinsic factor must be connected with the long-term failure of these orally administered combinations of vitamin B12 and intrinsic factor, but they cannot suggest an explanation. Wijrnenga,3 addressing the 1956 Hamburg conference on vitamin Bn and intrinsic factor, pointed out that there was evidence that intrinsic factor might be specific for each species, though it is known that activity is not limited to one species-for hog’s intrinsic factor is active in man. But he also cited some investigations suggesting that intrinsic-factor concentrates prepared from one species might contain substances that inhibit the absorption of vitamin B12 in other species. Williams et al.4 actually prepared intrinsic-factor fractions some of which augmented and some inhibited the absorption of vitamin B12’ judged by the Schilling test. Nevertheless physicians have had entirely satisfactory results from the treatment of pernicious anaemia over periods of many years by administration of relatively crude preparations of hog’s stomach. Thus Wilkinson 5 reported that of 441 patients treated for six or more years with preparations of desiccated hog’s stomach, only 15 relapsed ; these relapses occurred only because the patients neglected treatment and they responded promptly when given proper treatment again. The cause of the failure of the present intrinsic-factor concentrates may well lie in the method of preparation, and this needs to be fully explored as well as possible resistance, or inhibitors, arising because of the heterologous source of intrinsic factor. Meanwhile practitioners can take the hint and avoid these relatively very expensive oral preparations for the treatment of pernicious anaemia.
TRANQUILLISERS
AND SOCIETY abuse of tranquillisers has
CONCERN at the increasing been expressed by the W.H.O. Committee on Addictionproducing Drugs.6 In the U.S.A. in the first ten months of last year some 30,000 million tablets of one particular tranquillising drug are said to have been sold to the who public.- This figure is cited by Dickel and Dixon,7 " arising report 328 instances of " physical dangers from the treatment with tranquillisers of 8200 patients in the past eight years. The main thesis of Dickel and Dixon is that the dangers of abuse are altogether more subtle and pervasive than the occasional development of a skin rash or a blood dyscrasia. 8 They consider that such abuse has caused emotional, moral, and philosophical dangers to the patient ; dangers to medicine and the physician ; and dangers to the whole structure of society. In their experience, undesired emotional responses to tranquillising drugs occurred in 827 emotionally ill patients, whose condition was aggravated and distorted by these drugs. Equally disturbing were 1700 instances in which serious problems were created in the minds of essentially normal people by the misuse of tranquillisers. What very often 3. 4.
Wijmenga, H. G. In Vitamin B12 and Intrinsic Factor. Edited by H. C. Heinrich. Stuttgart, 1957; p. 156. Williams, W. L., Chow, B. F., Ellenbogen, L., Okuda, K. Ibid,
p. 250. 5. Wilkinson, J. F. Lancet, 1949, i, 291. 6. Tech. Rep. Wld Hlth Org. no. 116. 7. Dickel, H. A., Dixon, H. H. J. Amer. med. Ass. 8. See Lancet, Feb. 9, 1957, p. 308.
1957, 163,
422.
776
happened
was that a normal man went to his doctor for advice about a mildly distressing problem that had produced tension, worry, and anxiety. In place of advice and reassurance, the physician gave the latest tranquilliser. Commonly the drug produced not tranquillity but depression or other unwanted emotional reaction. The physician interpreted the new symptom as evidence of deep-seated mental illness, and the perplexed but essentially normal patient found himself classified as a serious mental case. Danger to the professional standards of medicine comes, Dickel and Dixon think, from the increasing tendency of doctors to prescribe, rather than to listen and diagnose, when confronted by a restless public, a growing pharmaceutical industry, an able advertising profession, and many truly anxious patients." Psychotherapy, they say, does not consist in writing prescriptions for tranquillisers, any more than the internist’s skill consists in prescribing the latest antibiotic. But the most insidious danger of all, according to Dickel and Dixon, is the sickness of a society which ranks the attainment of tranquillity, the freedom from anxiety, as its central aim. Throughout history " tension, alertness, alarmedness, fear, worry, anxiety and apprehension have been, are, and always will be important elements in the shaping of progress." But the new philosophy tells us that fear and anxiety are evidence of illness and require medical treatment with the latest soothing drug. "
ARTIFICIAL
PNEUMOTHORAX SxrrCE the temporary success of Cayley1 in 1885 and the permanent success of Forlanini2 in 1894, artificial pneumothorax (A.P.) has given many good results in pulmonary tuberculosis ; but severe complications have been commonenough to raise serious doubts about the true value of the method. In 1947 Rafferty 3 declared that the improperly used A.P. was more dangerous and lethal than thoracoplasty, the only difference being that the damage took longer to appear. There has always been a feeling that a balance must be struck between profit and loss-but that the loss was mainly due to mismanagement of the A.P. and could therefore be avoided. On the one hand, there were the hazards of too early induction in acute lesions ; on the other, there were risks in leaving it too late so that fibrosis and emphysema introduced other dangers. When longer bed rest and preliminary phrenic crush, with or without pneumoperitoneum, were used to counter the more serious consequences, results improved ; but effusion and atelectasis still ensued in some patients. Uncertainty remained, and the accumulating evidence about disappointing late results of A.P. did little to restore confidence. Nevertheless, an A.P. still had its attractions : it was easy to start and required little apparatus ; it avoided a major operation ; the patient’s assent, as a rule, was readily obtained ; and it had the merit of keeping the patient constantly under medical supervision, though often at the expense of lost working-time. Yet even before the advent of chemotherapy, the popularity of the A.P. was on the wane. Simmonds et al.4 recorded a decline in the number of A.p.s induced at Clare Hall Hospital from 1943 onwards; and chemotherapy, which might have been expected to restore the prestige of the A.p., in the event has not done Fewer inductions than ever are now perforrned and so. many physicians seem to be abandoning the method completely-as a result of personal experience and discussion with colleagues rather than because of published long-term results, which have always been hard to get. 1. 2. 3. 4.
London, Cayley, W. Middlesex Hospital Cayley Case Papers. 1885 ; vol. I, p. 50. Forlanini, C. Gazz. med. Ital., Torino, 1894, 45, 381. Rafferty, T. M. Artificial Pneumothorax in Pulmonary Tubereulosis. London, 1947. Simmonds, F. A. H., Laird, R., Macdonald, N. ii, 347.
Lancet, 1952,
In 1860 Walshe5 declared that there was " no warranty for the fanciful proposal to treat phthisis by producing artificial pnemnothorax " ; and many people would now agree with him. Chemotherapy can limit the complications of the A.P.,6—8 particularly pleural effusion; and Dixon9 has lately shown that the reduction is related to the duration of chemotherapy before induction. He thinks this development is an important advance in the history of pneumothorax, and so it is ; but the question many people will ask is how much does it matter ? The treat. ment of tuberculosis has changed fundamentally and it is now far from easy to justify the continued use of pneumo. thorax-a method which may conceivably reduce the Two years ago 10 we effectiveness of chemotherapy. the that the fate of A.P. would probably be suggested settled, not by a definitive controlled trial, but by the slow evolution of medical opinion ; and though at that time we had misgivings about letting the treatment drop into disuse without good reason, we cannot deny that opinion has further hardened against it. One of the few good words that are heard nowadays about the A.P. is that it is suitable for poorly developed countries where surgical conditions are primitive ; but this idea is dangerous, for the complications of A.P. often need major In such circumstances a surgery to overcome them. long period of continuous chemotherapy is safer, and probably more effective, without an A.P. ANTIGEN-ANTIBODY RESPONSES IN MULTIPLE SCLEROSIS FAMILIAR though we now are with the acute manifestations of allergic encephalomyelitis in laboratory animals, those most competent to judge have been reluctant to that a similar mechanism is implicated in assume multiple sclerosis. The clinical course of this condition, with its characteristic remissions, is one important reason for distinguishing it from the acute experimental disease. It is therefore of interest that in guineapigs and rabbits Bogdanove and Clark 11 have found that a further insult to the brain, delivered during the period of recovery from allergic encephalomyelitis, can induce histological changes of the same character at the site of damage. Such observations, if confirmed and extended, could bridge the gap by demonstrating that the acute disease confers on the central nervous system a form of tissue sensitivity which makes it vulnerable to further attacks. Another slant is suggested by a preliminary report from Honor Smith and her colleagues 12 on studies at Oxford which show that, on intrathecal injection of tuberculin, sensitised (Mantoux-positive) patients with multiple sclerosis react differently from other patients with the disease. About two years ago the investigators selected a group of 35 volunteers, all with multiple sclerosis of long standing, most of whom had been disabled for months or years. These were arranged in four groups according to their degree of sensitivity to the Mantoux test, and graded doses of purified protein derivative (r.p.D.) of tuberculin were given by the lumbar route. (A. control group of psychotic patients, in whom the meninges were otherwise normal, was used for comparison.) In patients with multiple sclerosis in whom the Mantoux test was negative the response to P.P.D. followed the normal pattern ; but in the Mantouxpositive groups the character of the reaction was clearly 5.
6. 7. 8. 9. 10. 11. 12.
Walshe,
W. H.
A Practical Treatise
on
the Diseases of the
Lungs. London, 1860 ; p. 314. Quoted by Marmion, T. Tubercle, 1957, 38, 63. H. B. 288. Tubercle, 1952, 33, Wright, Birath, G. Dis. Chest, 1953, 24, 245. Scadding, J. G. Lancet, 1955, ii, 154. Dixon, W. M. Tubercle, 1957, 38, 21. See loading article, Lancet, 1955, ii, 26. Bogdanove, L. H., Clark, G. J. Neuropath. 1957, 16, 57. Smith, H. V., Espir, M. L. E., Whitty, C. W. M., Russell, W. R. J. Neurol. Psychiat. 1957, 20, 1.