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THE MEDICAL USES OF RADIUM.
1231 to war, and that the Army will never be held up for expected supplies. The section has also in mind the danger of accumulating a large surplus of stores which, if thrown on the market, must disorganise industry in the difficult post-war days. Such forcsight is astonishing. ____
A VACCINATION
INQUIRY.
IN an address delivered before the Berne Medical Club, Dr. A. Hauswirth, the medical officer of health for that city, reports that a committee consisting of two medical men, including himself as chairman, and three laymen, one of whom was an antivaccinationist. and the other two opponents of all compulsory measures though alive to the advantages of vaccination, was appointed by the Berne City Council to inquire into the supposed evil effects of vaccination among approximately 40,000 persons who had been compulsorily vaccinated between the spring of 1922 and the autumn of 1924 on the occasion of a small-pox epidemic. Only 14 cases in all were reported to the committee which after a careful investigation found that there were only four cases in which a possibility or probability of a connexion between the disease and the previous vaccination could not be excluded. The first case was that of encephalitis lethargica in a youth aged 17, who developed the symptoms shortly after vaccination. and made an almost complete recovery. The second case was one of fatal septicaemia following measles which occurred in a girl aged 9 years, vaccinated on the third or fourth day of the incnbation period. In the third case a girl aged 14, six days after vaccination, developed follicular tonsillitis, followed by fatal septicsemia. The fourth case was that of a boy aged 13, who was vaccinated six days after recovery from an acute
gastro-intestinal attack, accompanied by circulatory disturbance. About a week later symptoms of acute septicaemia developed, and death took place. The three deaths, therefore, were due to septic processes, in which the onset of the disease probably coincided with the performance of vaccination. The lesson to be learnt from these cases is that on the slightest suspicion of an acute infective or other acute disease vaccination should not be performed. In conclusion, Dr. Hauswirth remarks that as in only 0-01 per cent., or in 1 out of 10,000 vaccinations, could any evil effect be attributed to the process, the occurrence of such cases is far outweighed by the enormous benefit conferred by the absolute protection against small-pox provided by vaccination.
oil soap.
These experiments led Prof. Larson to the possibility of obtaining non-pathogenic strains of other bacilli. He was able to give detoxicated pneumococci to rabbits in doses which would have been certainly lethal without the admixture of soap, and he even succeeded in immunising guineapigs to tetanus, at the same time bringing evidence to support Ehrlich’s theory that the more sensitive an animal is to a given toxin the greater will be its antibody formation in response to that toxin. All bacterial toxins, he found, can be detoxicated by this method without losing their immunising property, the only exception being that produced by B. botulinus. The first human volunteers were treated with a 1/10 L. + dose of diphtheria toxin in 1 per cent. castor oil soap, but it was found that the same dose in 2 per cent. soap gave less reaction. The latter mixture was used on 800 medical students, and over 60 per cent. of Schick-positive reactors became Schick-negative within 10 days. Applying the same principle to scarlet fever toxin (Dick), he found that a 3000 skin-test dose could be covered with 2 per cent. soap. This solution causes some reactions in adults, for whom a 3 per cent. soap solution is found to be more satisfactory. This dose immunises 90 per cent. of positive reactors within three weeks, and has been used as a prophylactic in various institutional outbreaks, apparently with success. As a method of prophylaxis it has none of the unpleasant concomitants of passive immunisation with Dochez More recently a combined scarlet fever and serum. diphtheria saponified (3 per cent.) toxin has been used; this is said to cause less reaction than the separate use of two saponified toxins. It should be added that Prof. Larson has been able to recover the toxin from his solutions by adding a simple salt solution, and has thus satisfied himself that there is no truth in the suggestion that the toxin is destroyed by soap. At present he recommends that two doses of the combined toxins be given at an interval of two to four weeks. Five thousand school-children in Minneapolis were given the first dose recently, and there was only one complaint-of a sore arm. The discussion which followed Prof. Larson’s address was led by Dr. Roger G. Perkins, professor of hygiene at Western Reserve University, who described the successful use of Prof. Larson’s toxin in Cleveland, and uttered a warning against allowing the public to believe that biological methods would ever be successful in 100 per cent. of cases. Dr. Peters described successful arrest of epidemics of scarlet fever in Cincinnati by the use of the same toxin, and other speakers also gave personal testimony to its efficacy in practice. In answer to inquiries about the possibility of obtaining the toxin, Prof. Larson said that he had sent out over 50,000 doses of scarlet fever toxin, and that the present demand was beyond the means of a teaching institution. He has therefore instructed one of the large commercial houses in his technique, and his material will soon be on the market.
investigate
SAPONIFIED TOXIN IN SCARLET FEVER. Prof. W. P. Larson, of Minnesota University, attended a meeting of health officers of the State of Ohio in the middle of last month, and gave an account of his method of detoxicating toxin and the results which he has had in producing active immunity against scarlet fever and diphtheria. Two years ago he was investigating the cause of pellicle formation in bacterial cultures, and to test his theory that THE MEDICAL USES OF RADIUM. surface tension rather than the presence of oxygen THE stock of radium salt entrusted by H.M. is the determining factor in this phenomenon, he introduced soap solutions into the culture media. Government to the Medical Research Council is being Finding the appropriate concentration of soap, he used at 11 centres, distributed through the country, was able to make all pellicle-forming organisms grow for the treatment of disease. Every year these centres either in the liquid medium or at the bottom of the furnish a report of their activities to the Radiology flask. The critical surface tension above which Committee, appointed jointly by the Council and the pellicle formation will always occur he found to be British Empire Cancer Campaign, which body has 42 dynes. Non-pellicle formers can be made to form added to the stock of available radium, and on this pellicles if they will grow on a glycerine medium, committee falls the difficult duty of collating the and convert the glycerine into fatty bodies. Inci- reports-diverse as to manner as well as matterdentally he observed that the tubercle bacillus loses into a readable account of progress made. This its pathogenicity when grown on low-tension media year, in No. 112 of the special report series,t which instead of as a pellicle, and he claims that by using contains reports on cancer of the breast, uterus, a medium containing soap he can produce in a few mouth, nasopharynx and larynx, oesophagus, rectum, days cultures similar to the B.C.G. cultures which bladder, and prostate, no reference is made to the Calmette obtains by growing tubercle bacilli in bile treatment of rodent ulcer or to non-malignant conmedium for 13 years. The soap found most suit- ditions. The reason given for these omissions is able as regards viscosity is a highly purified castor that suitable radiological treatment for the former ____
1 Schweizerische medizinische Wochenschrift, Nov. 20th, 1926.
1 H.M. Stationery Office, 1926, pp. 34, is. 6d.
1232 and for many non-malignant diseases is now well known. The technique adopted by common consent at the centres in the treatment of menorrhagia is also considered to have reached a stage which carries it beyond urgent need of further research. The benefit conferred by radium on those suffering from the leukaemias is now known to be short-lived, the blood picture soon becoming abnormal again. The section of this report which is of most interest is that on cancer of the cervix, since a brief account of the technique used at each of the centres is supplied, and an analysis has been made of statistical data, collected from four of the centres, of patients treated since 1922. Of 214 cases, with few exceptions inoperable, 120 are dead and 36 have not been traced. At a period not less than a year after treatment 31 were alive but not free of disease, while 27 were apparently well. Of 20 borderline or operable cases the corresponding numbers were 4, 4, 6, and 6. From the accounts of technique it is obvious that there is still a considerable degree of variation in the dosage of radium used and in the manner of its application. The introduction of 50-100 mg. into the cervical canal for 22 to 24 hours is a measure common to all except St. Bartholomew’s Hospital, where a study of the effects of much smaller quantities acting continuously for six days is being made. Growths which cannot adequately be reached by radium tubes in the cervical canal are treated in some centres by packing applicators round the tissues involved, while others insert needles into the growth, care being taken to avoid proximity to rectum or bladder. In spite of these differences there seems to be more hope of soon establishing a standard technique in cancer of the cervix than in most other regions. Once this has been agreed on, it will be less difficult to ascertain the scope of radiotherapy, and especially to decide whether it should be advocated as a substitute for excision of the growth in operable cases or only as an ancillary measure to prevent recurrence.
Modern Technique in Treatment. A Series of Special Articles, contributed by invitation, on the Treatment of Medical and Surgical Conditions.
CCI.-THE TREATMENT OF CHILBLAIN
(ERYTHEMA PERNIO).* II.-THE MANAGEMENT OF THE CASE. FROM what was said in the preliminary considerations of the aetiology of chilblains and of those susceptible to them, it will be clear that their treatment must vary according to the type of patient with which one has to deal, and should, whenever possible, be preceded by a thorough physical examination. In particular it is necessary to search for any chronic infection which may be lowering the patient’s resistance-for example, tuberculosis of lymphatic glands or other organs, persistent nasopharyngeal catarrh, nasal-sinus disease, septic tonsils, or oral sepsis. There are points about the general treatment of patients with a tendency to chilblains which are applicable to all cases. Unfortunately, however, among the majority these are seldom practicable for social and financial reasons.
Diet and Exercise. modern knowledge of biochemistry and bacteriology-incomplete as it is-the rational rules of diet are so obvious as to be almost platitudinous. Briefly the indications in these patients are : (1) To modify the diet according to the patient’s mode of life ; the more sedentary the latter the less should be the amount of carbohydrate taken. (2) To ensure an adequate supply of fresh food containing mineral salts and vitamins ; green vegeWith
*
An
our
article
on
the
Considerations-appeared
Treatment of Chilblains-I. General in this series last week.
tables and mixed salads, fruit, particularly wholemeal or Swedish bread with plenty of
apples, butter,
eggs, preferably raw, milk, cheese, cream, and a moderate quantity of freshly cooked meat and fish should form the basis of a normal diet. With regard to fruit, however, the decalcifying action of certain very acid fruits should be remembered. (3) In patients with symptoms of excessive intestinal putrefaction the amount of meat and fish should, of course, be reduced to a minimum and the quantity of carbohydrate and fresh vegetables and fruit increased. (4) Conversely in those with intestinal fermentation and excessive acid production, all soft starchy and concentrated sweet foods must be excluded. The great majority of these patients have been or are being, wrongly fed, the common fault being an excess of carbohydrate and a lack of fresh dairy produce and uncooked vegetables and fruit. It is clear that physical exercise, preferably out of doors, provides the best method of improving a sluggish peripheral circulation, but, of course, the amount taken must be regulated by the patient’s physique, and the presence or absence of a chronic infection-tuberculous or otherwise-must be taken into account. Jacquet’s biokinetic method of treating chilblains, if conscientiously carried out, is of value. The patient fixes the finger- or toe-joints by forcible muscular effort, and holds them extended in an elevated position for five minutes several times daily.
Sunlight. Except in rare cases chilblains disappear spontaneously in summer, and are much less common in a cold dry atmosphere than in damp chilly weather, Apart from this, heliotherapy and, to a less extent. artificial light baths are of great value in the treatment of patients with acrocyanosis. I have, however, seen a patient with lupus erythematosus develop while under intensive treatment with carbon-arc light baths. The beneficial action of ultra-violet light in these cases is probably complex. It undoubtedly affects the vasomotor system as well as other parts of the sympathetic nervous system-viz., that controlling the pigmentation of the skin. the fibres supplying the hair-bulbs, and those responsible for muscle-tone. Many patients state that after a course of heliotherapy or light baths they " feel the cold " far less. Apart from increasing vasomotor tone ultra-violet radiations act on the endocrine glands, particularly on the thyroid and parathyroids, but also on the ovaries and testes. As regards chilblains it is probable that the action of ultra-violet light on the sympathetic and certain of the endocrine glands is chiefly responsible for its beneficial effect, but its power of raising the calcium concentration in the blood may in some cases be an important factor, and in this connexion it is of interest that the experiments of Grant and Gates of the Rockefeller Institute (quoted by Howard Humphris 1), appear to show that the parathyroids are more profoundly affected by ultra-violet radiation than the other endocrine glands.
chilblains
Clothing. lothing.
Too little importance is unfortunately attached to the question of clothing by the medical profession, and it is a sad reflection that the emancipation of women from the unhygienic frills and furbelows of the Victorian age lies to the credit of the modern costumier and not to ours. It is high time that our more conservative tailors and hosiers condemned the Eton suit, the heavy tweeds, and winter underclothing to oblivion. Fortunately the system of compulsory games that obtains at preparatory and public schools ensures that boys wear a rational costume for, at any rate, part of their daily life. Needless to say. a patient subject to chilblains should be advised to keep the extremities warm with loose woollen gloves and stockings, but the rest of the clothing should be light and porous, and whenever possible vigorous out1 Artificial Sunlight and its Therapeutic Uses, Oxford Med. 3rd edit., p. 71.
Pub.,
A VACCINATION
INQUIRY.
IN an address delivered before the Berne Medical Club, Dr. A. Hauswirth, the medical officer of health for that city, reports that a committee consisting of two medical men, including himself as chairman, and three laymen, one of whom was an antivaccinationist. and the other two opponents of all compulsory measures though alive to the advantages of vaccination, was appointed by the Berne City Council to inquire into the supposed evil effects of vaccination among approximately 40,000 persons who had been compulsorily vaccinated between the spring of 1922 and the autumn of 1924 on the occasion of a small-pox epidemic. Only 14 cases in all were reported to the committee which after a careful investigation found that there were only four cases in which a possibility or probability of a connexion between the disease and the previous vaccination could not be excluded. The first case was that of encephalitis lethargica in a youth aged 17, who developed the symptoms shortly after vaccination. and made an almost complete recovery. The second case was one of fatal septicaemia following measles which occurred in a girl aged 9 years, vaccinated on the third or fourth day of the incnbation period. In the third case a girl aged 14, six days after vaccination, developed follicular tonsillitis, followed by fatal septicsemia. The fourth case was that of a boy aged 13, who was vaccinated six days after recovery from an acute
gastro-intestinal attack, accompanied by circulatory disturbance. About a week later symptoms of acute septicaemia developed, and death took place. The three deaths, therefore, were due to septic processes, in which the onset of the disease probably coincided with the performance of vaccination. The lesson to be learnt from these cases is that on the slightest suspicion of an acute infective or other acute disease vaccination should not be performed. In conclusion, Dr. Hauswirth remarks that as in only 0-01 per cent., or in 1 out of 10,000 vaccinations, could any evil effect be attributed to the process, the occurrence of such cases is far outweighed by the enormous benefit conferred by the absolute protection against small-pox provided by vaccination.
oil soap.
These experiments led Prof. Larson to the possibility of obtaining non-pathogenic strains of other bacilli. He was able to give detoxicated pneumococci to rabbits in doses which would have been certainly lethal without the admixture of soap, and he even succeeded in immunising guineapigs to tetanus, at the same time bringing evidence to support Ehrlich’s theory that the more sensitive an animal is to a given toxin the greater will be its antibody formation in response to that toxin. All bacterial toxins, he found, can be detoxicated by this method without losing their immunising property, the only exception being that produced by B. botulinus. The first human volunteers were treated with a 1/10 L. + dose of diphtheria toxin in 1 per cent. castor oil soap, but it was found that the same dose in 2 per cent. soap gave less reaction. The latter mixture was used on 800 medical students, and over 60 per cent. of Schick-positive reactors became Schick-negative within 10 days. Applying the same principle to scarlet fever toxin (Dick), he found that a 3000 skin-test dose could be covered with 2 per cent. soap. This solution causes some reactions in adults, for whom a 3 per cent. soap solution is found to be more satisfactory. This dose immunises 90 per cent. of positive reactors within three weeks, and has been used as a prophylactic in various institutional outbreaks, apparently with success. As a method of prophylaxis it has none of the unpleasant concomitants of passive immunisation with Dochez More recently a combined scarlet fever and serum. diphtheria saponified (3 per cent.) toxin has been used; this is said to cause less reaction than the separate use of two saponified toxins. It should be added that Prof. Larson has been able to recover the toxin from his solutions by adding a simple salt solution, and has thus satisfied himself that there is no truth in the suggestion that the toxin is destroyed by soap. At present he recommends that two doses of the combined toxins be given at an interval of two to four weeks. Five thousand school-children in Minneapolis were given the first dose recently, and there was only one complaint-of a sore arm. The discussion which followed Prof. Larson’s address was led by Dr. Roger G. Perkins, professor of hygiene at Western Reserve University, who described the successful use of Prof. Larson’s toxin in Cleveland, and uttered a warning against allowing the public to believe that biological methods would ever be successful in 100 per cent. of cases. Dr. Peters described successful arrest of epidemics of scarlet fever in Cincinnati by the use of the same toxin, and other speakers also gave personal testimony to its efficacy in practice. In answer to inquiries about the possibility of obtaining the toxin, Prof. Larson said that he had sent out over 50,000 doses of scarlet fever toxin, and that the present demand was beyond the means of a teaching institution. He has therefore instructed one of the large commercial houses in his technique, and his material will soon be on the market.
investigate
SAPONIFIED TOXIN IN SCARLET FEVER. Prof. W. P. Larson, of Minnesota University, attended a meeting of health officers of the State of Ohio in the middle of last month, and gave an account of his method of detoxicating toxin and the results which he has had in producing active immunity against scarlet fever and diphtheria. Two years ago he was investigating the cause of pellicle formation in bacterial cultures, and to test his theory that THE MEDICAL USES OF RADIUM. surface tension rather than the presence of oxygen THE stock of radium salt entrusted by H.M. is the determining factor in this phenomenon, he introduced soap solutions into the culture media. Government to the Medical Research Council is being Finding the appropriate concentration of soap, he used at 11 centres, distributed through the country, was able to make all pellicle-forming organisms grow for the treatment of disease. Every year these centres either in the liquid medium or at the bottom of the furnish a report of their activities to the Radiology flask. The critical surface tension above which Committee, appointed jointly by the Council and the pellicle formation will always occur he found to be British Empire Cancer Campaign, which body has 42 dynes. Non-pellicle formers can be made to form added to the stock of available radium, and on this pellicles if they will grow on a glycerine medium, committee falls the difficult duty of collating the and convert the glycerine into fatty bodies. Inci- reports-diverse as to manner as well as matterdentally he observed that the tubercle bacillus loses into a readable account of progress made. This its pathogenicity when grown on low-tension media year, in No. 112 of the special report series,t which instead of as a pellicle, and he claims that by using contains reports on cancer of the breast, uterus, a medium containing soap he can produce in a few mouth, nasopharynx and larynx, oesophagus, rectum, days cultures similar to the B.C.G. cultures which bladder, and prostate, no reference is made to the Calmette obtains by growing tubercle bacilli in bile treatment of rodent ulcer or to non-malignant conmedium for 13 years. The soap found most suit- ditions. The reason given for these omissions is able as regards viscosity is a highly purified castor that suitable radiological treatment for the former ____
1 Schweizerische medizinische Wochenschrift, Nov. 20th, 1926.
1 H.M. Stationery Office, 1926, pp. 34, is. 6d.
1232 and for many non-malignant diseases is now well known. The technique adopted by common consent at the centres in the treatment of menorrhagia is also considered to have reached a stage which carries it beyond urgent need of further research. The benefit conferred by radium on those suffering from the leukaemias is now known to be short-lived, the blood picture soon becoming abnormal again. The section of this report which is of most interest is that on cancer of the cervix, since a brief account of the technique used at each of the centres is supplied, and an analysis has been made of statistical data, collected from four of the centres, of patients treated since 1922. Of 214 cases, with few exceptions inoperable, 120 are dead and 36 have not been traced. At a period not less than a year after treatment 31 were alive but not free of disease, while 27 were apparently well. Of 20 borderline or operable cases the corresponding numbers were 4, 4, 6, and 6. From the accounts of technique it is obvious that there is still a considerable degree of variation in the dosage of radium used and in the manner of its application. The introduction of 50-100 mg. into the cervical canal for 22 to 24 hours is a measure common to all except St. Bartholomew’s Hospital, where a study of the effects of much smaller quantities acting continuously for six days is being made. Growths which cannot adequately be reached by radium tubes in the cervical canal are treated in some centres by packing applicators round the tissues involved, while others insert needles into the growth, care being taken to avoid proximity to rectum or bladder. In spite of these differences there seems to be more hope of soon establishing a standard technique in cancer of the cervix than in most other regions. Once this has been agreed on, it will be less difficult to ascertain the scope of radiotherapy, and especially to decide whether it should be advocated as a substitute for excision of the growth in operable cases or only as an ancillary measure to prevent recurrence.
Modern Technique in Treatment. A Series of Special Articles, contributed by invitation, on the Treatment of Medical and Surgical Conditions.
CCI.-THE TREATMENT OF CHILBLAIN
(ERYTHEMA PERNIO).* II.-THE MANAGEMENT OF THE CASE. FROM what was said in the preliminary considerations of the aetiology of chilblains and of those susceptible to them, it will be clear that their treatment must vary according to the type of patient with which one has to deal, and should, whenever possible, be preceded by a thorough physical examination. In particular it is necessary to search for any chronic infection which may be lowering the patient’s resistance-for example, tuberculosis of lymphatic glands or other organs, persistent nasopharyngeal catarrh, nasal-sinus disease, septic tonsils, or oral sepsis. There are points about the general treatment of patients with a tendency to chilblains which are applicable to all cases. Unfortunately, however, among the majority these are seldom practicable for social and financial reasons.
Diet and Exercise. modern knowledge of biochemistry and bacteriology-incomplete as it is-the rational rules of diet are so obvious as to be almost platitudinous. Briefly the indications in these patients are : (1) To modify the diet according to the patient’s mode of life ; the more sedentary the latter the less should be the amount of carbohydrate taken. (2) To ensure an adequate supply of fresh food containing mineral salts and vitamins ; green vegeWith
*
An
our
article
on
the
Considerations-appeared
Treatment of Chilblains-I. General in this series last week.
tables and mixed salads, fruit, particularly wholemeal or Swedish bread with plenty of
apples, butter,
eggs, preferably raw, milk, cheese, cream, and a moderate quantity of freshly cooked meat and fish should form the basis of a normal diet. With regard to fruit, however, the decalcifying action of certain very acid fruits should be remembered. (3) In patients with symptoms of excessive intestinal putrefaction the amount of meat and fish should, of course, be reduced to a minimum and the quantity of carbohydrate and fresh vegetables and fruit increased. (4) Conversely in those with intestinal fermentation and excessive acid production, all soft starchy and concentrated sweet foods must be excluded. The great majority of these patients have been or are being, wrongly fed, the common fault being an excess of carbohydrate and a lack of fresh dairy produce and uncooked vegetables and fruit. It is clear that physical exercise, preferably out of doors, provides the best method of improving a sluggish peripheral circulation, but, of course, the amount taken must be regulated by the patient’s physique, and the presence or absence of a chronic infection-tuberculous or otherwise-must be taken into account. Jacquet’s biokinetic method of treating chilblains, if conscientiously carried out, is of value. The patient fixes the finger- or toe-joints by forcible muscular effort, and holds them extended in an elevated position for five minutes several times daily.
Sunlight. Except in rare cases chilblains disappear spontaneously in summer, and are much less common in a cold dry atmosphere than in damp chilly weather, Apart from this, heliotherapy and, to a less extent. artificial light baths are of great value in the treatment of patients with acrocyanosis. I have, however, seen a patient with lupus erythematosus develop while under intensive treatment with carbon-arc light baths. The beneficial action of ultra-violet light in these cases is probably complex. It undoubtedly affects the vasomotor system as well as other parts of the sympathetic nervous system-viz., that controlling the pigmentation of the skin. the fibres supplying the hair-bulbs, and those responsible for muscle-tone. Many patients state that after a course of heliotherapy or light baths they " feel the cold " far less. Apart from increasing vasomotor tone ultra-violet radiations act on the endocrine glands, particularly on the thyroid and parathyroids, but also on the ovaries and testes. As regards chilblains it is probable that the action of ultra-violet light on the sympathetic and certain of the endocrine glands is chiefly responsible for its beneficial effect, but its power of raising the calcium concentration in the blood may in some cases be an important factor, and in this connexion it is of interest that the experiments of Grant and Gates of the Rockefeller Institute (quoted by Howard Humphris 1), appear to show that the parathyroids are more profoundly affected by ultra-violet radiation than the other endocrine glands.
chilblains
Clothing. lothing.
Too little importance is unfortunately attached to the question of clothing by the medical profession, and it is a sad reflection that the emancipation of women from the unhygienic frills and furbelows of the Victorian age lies to the credit of the modern costumier and not to ours. It is high time that our more conservative tailors and hosiers condemned the Eton suit, the heavy tweeds, and winter underclothing to oblivion. Fortunately the system of compulsory games that obtains at preparatory and public schools ensures that boys wear a rational costume for, at any rate, part of their daily life. Needless to say. a patient subject to chilblains should be advised to keep the extremities warm with loose woollen gloves and stockings, but the rest of the clothing should be light and porous, and whenever possible vigorous out1 Artificial Sunlight and its Therapeutic Uses, Oxford Med. 3rd edit., p. 71.
Pub.,