1
97 Cabot has the credit of first calling attention to a condition which he described under the heading, <; The Lymphocytosis of Infection." His first case was that of a septic infection of the finger followed by lymphangitis and enlargement of axillary glands. The blood changes are not given in detail, but a statement from Cabot that there was " throughout a ’’ well-marked, absolute and relative lymphocytosis has more value than mere figures. Fever continued for " several weeks," but the patient recovered and was in good health 15 years later. This is not the picture of leukaemia, nor is it that of glandular fever. Yet Dr. Tidy says that " glandular fever and the condition described as infective mononucleosis are identical." There is a further aspect of the question which may be considered-namely, that there exists an infective myelocytosis-e.g., that recorded by Simon &mdash;which would appear to bear much the same relation to myelaemia as infective lymphocytosis does to lymphaemia. There are good reasons for supposing that a hyperplasia of the haemopoietic tissues, com- parable to that of leukaemia in all but degree, may complicate various septic conditions, and is further of such frequent occurrence as to be typical in mumps (in early years of life) and in glandular fever. But it may be doubted whether the recorded cases warrant any more sweeping assertion than this. I am, Sir, yours faithfully, Sevenoaks, Kent, July 6th, 1923. GORDON WARD. TUBERCLE ANTIGENS. To the Editor of THE LANCET. SIR,-In your issue of June 30th you draw attention editorially to recent work of Dr. A. R. Jentzer and his fellow-workers regarding the attack on the acid-fast coat of the tubercle bacillus in vivo. These workers inject or use a proprietary preparation or compound of fats, lipoids, and waxes. Prof. G. Dreyer, as is well known, removes the fatty and waxy capsule of the tubercle bacillus in vitro by formalin-acetone. In both the methods centre on the waxy and fatty protective coat. According to Dreyer, the removal of the acid-fast substances releases the protein antigen. This is thus more readily soluble in trypsin, and after injection is more effective in the production of various antibodies. On the other hand, according to Jentzer and his colleagues, it is claimed that their compound of fatty and waxy substances " stimulate the tissues to produce ferments which not only saponify the fatty and waxy substances introduced by parenteral injection, but- also the fatty, lipoid, and waxy con- stituents of the tubercle bacillus." This method of attacking tuberculosis is described as novel, and in a sense to some extent as anticipating the work of Prof. Dreyer, but the exact composition and mode of manufacture of the compound of the fats, lipoids, and waxy substances used by Jentzer and his colleagues are not published. May I point out that the employment of the fats and lipoids and the theory therefrom constructed is not novel ? P For many years various aspects of the fat-splitting action of the pancreas has occupied my attention. The results of my work, I carried out in the physiological and bacteriological I laboratories, King’s College, have been published in ’THE LANCET and elsewhere. 2 The main outcome of this work has been to show that a natural and increased production of lipase in the blood and tissues is an important factor in the protective mechanism of the body. This is particularly the case in malignant disease, although I have pointed out that this lipolytic defensive response is not specific to cancer but is common to tuberculosis and other bacterial invasions. This I have expressed in identically the same terms as employed by Jentzer and his colleagues. Lipase, moreover, lends itself naturally to attacking the fatty 1 Amer. Jour. Med. Sci., 1907, cxxxlii., 389. 2 Shaw-Mackenzie, J. A.: THE LANCET, 1919, ii., 825; Brit. Med. Jour., 1921, i., 402 ; Jour. Trop. Med. and Hyg., 1921, xxiv., 161 ; Med. Press and Circ., 1922, i., 287. and lipoid coat of the tubercle bacillus in vitro. As long known, lecithin is split by lipase and accelerates also the activity of that enzyme in vitro and in vivo. In my experiments it was found that fatty acids are liberated by lipase from killed tubercle bacilli in vitro. In this way saponified extracts were prepared and indicated for therapeutic use. Preparations were made also by extracting tuberculous material with the usual fat and lipoid solvents, alcohol, ether, and chloroform successively, in a Soxhlet’s apparatus in the usual way, and saponifying the extracted material or emulsifying. This method in the main differs essentially from that of Jentzer and his colleagues in that the products of the fats and lipoids of tubercle bacilli are used, together with protein and phosphate derivatives or constituents of the bacillus. The soaps themselves&mdash;e.g., sodium oleate, organic and inorganic phosphates, and proteins-have marked power in stimulating tissue lipolytic activity. Similar methods have been employed in dealing with the fats and lipoids of the cancer cell and tissues. The idea or principle underlying treatment by these extracts is stimulation of tissue lipolytic activity with destructive action on the fats and lipoids of the cancer cell, as in the case of tuberculosis, on the fats and lipoids of the tubercle bacillus. I am, Sir, yours faithfully, J. A. SHAW-MACKENZIE, M.D. Lond. London, June 30th, 1923. DELAY IN GIVING DIPHTHERIA ANTITOXIN. To the Editor of THE LANCET. SiR,-All medical officers of health will agree with Dr. F. F. Caiger that frequently in fatal cases valuable time is lost by the practitioner. In 17 fatal cases of diphtheria occurring in Brighton during 1921 and 1922 the time lost by the doctor failing to diagnose the condition is shown in the following table :- There is little doubt from a study of the table that the case mortality of diphtheria can be greatly reduced by prompt diagnosis and immediate removal of the patient to hospital. In Brighton probably one-third of the deaths could have been avoided ; assuming the same conditions for the whole of England and Wales the annual loss due to lack of prompt diagnosis by the doctor is some 1800 lives. When one considers that diphtheria in the child is easy to diagnose, also that negative swab results give little help, the folly of awaiting swab results is apparent. My own conclusions are : (1) It is the duty of general practitioners to acquaint themselves with the easily-grasped clinical signs of diphtheria and the duty of those controlling fever hospitals to give e opportunity to the general practitioner to see typical cases of the disease ; (2) it is doubtful if local authorities should accept swabs for the diagnosis of acute throat conditions in children. I am, Sir, yours faithfully, July 3rd, 1923. DUNCAN FORBES, Medical Officer of Health, Brighton. R.A.M.C. MEMORIAL IN DUBLIN.-On July 4th Sir John Goodwin, Director-General of the Army Medical Service, unveiled in St. Patrick’s Cathedral, Dublin, a memorial to the officers and men of the Royal Army Medical Corps who fell in the late war. The memorial is a marble tablet, a replica of that erected some months ago in West- minster Abbey. There was a large attendance at the unveiling ceremony.

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97

Cabot has the credit of first calling attention to acondition which he described under the heading,<; The Lymphocytosis of Infection." His first casewas that of a septic infection of the finger followed bylymphangitis and enlargement of axillary glands.The blood changes are not given in detail, but astatement from Cabot that there was " throughout a

’’

well-marked, absolute and relative lymphocytosishas more value than mere figures. Fever continuedfor " several weeks," but the patient recovered andwas in good health 15 years later. This is not thepicture of leukaemia, nor is it that of glandular fever.Yet Dr. Tidy says that " glandular fever and thecondition described as infective mononucleosis are

identical." There is a further aspect of the questionwhich may be considered-namely, that there existsan infective myelocytosis-e.g., that recorded bySimon &mdash;which would appear to bear much the samerelation to myelaemia as infective lymphocytosis doesto lymphaemia. There are good reasons for supposingthat a hyperplasia of the haemopoietic tissues, com-parable to that of leukaemia in all but degree, maycomplicate various septic conditions, and is furtherof such frequent occurrence as to be typical in mumps(in early years of life) and in glandular fever.But it may be doubted whether the recorded cases

warrant any more sweeping assertion than this.I am, Sir, yours faithfully,

Sevenoaks, Kent, July 6th, 1923. GORDON WARD.

TUBERCLE ANTIGENS.

To the Editor of THE LANCET.

SIR,-In your issue of June 30th you draw attentioneditorially to recent work of Dr. A. R. Jentzer and hisfellow-workers regarding the attack on the acid-fastcoat of the tubercle bacillus in vivo. These workersinject or use a proprietary preparation or compound offats, lipoids, and waxes. Prof. G. Dreyer, as is wellknown, removes the fatty and waxy capsule of thetubercle bacillus in vitro by formalin-acetone. Inboth the methods centre on the waxy and fattyprotective coat. According to Dreyer, the removal ofthe acid-fast substances releases the protein antigen.This is thus more readily soluble in trypsin, and afterinjection is more effective in the production of variousantibodies. On the other hand, according to Jentzerand his colleagues, it is claimed that their compound offatty and waxy substances " stimulate the tissues toproduce ferments which not only saponify the fattyand waxy substances introduced by parenteralinjection, but- also the fatty, lipoid, and waxy con-stituents of the tubercle bacillus." This method ofattacking tuberculosis is described as novel, and in asense to some extent as anticipating the work ofProf. Dreyer, but the exact composition and mode ofmanufacture of the compound of the fats, lipoids, andwaxy substances used by Jentzer and his colleagues arenot published. May I point out that the employmentof the fats and lipoids and the theory therefromconstructed is not novel ? P For many years variousaspects of the fat-splitting action of the pancreas hasoccupied my attention. The results of my work, Icarried out in the physiological and bacteriological Ilaboratories, King’s College, have been published in’THE LANCET and elsewhere. 2 The main outcome ofthis work has been to show that a natural and increasedproduction of lipase in the blood and tissues is animportant factor in the protective mechanism of thebody. This is particularly the case in malignantdisease, although I have pointed out that this lipolyticdefensive response is not specific to cancer but iscommon to tuberculosis and other bacterial invasions.This I have expressed in identically the same terms asemployed by Jentzer and his colleagues. Lipase,moreover, lends itself naturally to attacking the fatty

1 Amer. Jour. Med. Sci., 1907, cxxxlii., 389.2 Shaw-Mackenzie, J. A.: THE LANCET, 1919, ii., 825;

Brit. Med. Jour., 1921, i., 402 ; Jour. Trop. Med. and Hyg., 1921,xxiv., 161 ; Med. Press and Circ., 1922, i., 287.

and lipoid coat of the tubercle bacillus in vitro. Aslong known, lecithin is split by lipase and acceleratesalso the activity of that enzyme in vitro and in vivo.In my experiments it was found that fatty acids areliberated by lipase from killed tubercle bacilli in vitro.In this way saponified extracts were prepared andindicated for therapeutic use. Preparations were

made also by extracting tuberculous material with theusual fat and lipoid solvents, alcohol, ether, andchloroform successively, in a Soxhlet’s apparatus inthe usual way, and saponifying the extracted materialor emulsifying. This method in the main differsessentially from that of Jentzer and his colleagues inthat the products of the fats and lipoids of tuberclebacilli are used, together with protein and phosphatederivatives or constituents of the bacillus. The

soaps themselves&mdash;e.g., sodium oleate, organic andinorganic phosphates, and proteins-have markedpower in stimulating tissue lipolytic activity. Similarmethods have been employed in dealing with the fatsand lipoids of the cancer cell and tissues. The idea orprinciple underlying treatment by these extracts isstimulation of tissue lipolytic activity with destructiveaction on the fats and lipoids of the cancer cell, as inthe case of tuberculosis, on the fats and lipoids of thetubercle bacillus.

I am, Sir, yours faithfully,J. A. SHAW-MACKENZIE, M.D. Lond.

London, June 30th, 1923.

DELAY IN GIVING DIPHTHERIA ANTITOXIN.To the Editor of THE LANCET.

SiR,-All medical officers of health will agree withDr. F. F. Caiger that frequently in fatal cases valuabletime is lost by the practitioner. In 17 fatal cases ofdiphtheria occurring in Brighton during 1921 and 1922the time lost by the doctor failing to diagnose thecondition is shown in the following table :-

There is little doubt from a study of the table thatthe case mortality of diphtheria can be greatlyreduced by prompt diagnosis and immediate removalof the patient to hospital. In Brighton probablyone-third of the deaths could have been avoided ;assuming the same conditions for the whole of Englandand Wales the annual loss due to lack of promptdiagnosis by the doctor is some 1800 lives. Whenone considers that diphtheria in the child is easyto diagnose, also that negative swab results give littlehelp, the folly of awaiting swab results is apparent.My own conclusions are : (1) It is the duty of

general practitioners to acquaint themselves with theeasily-grasped clinical signs of diphtheria and theduty of those controlling fever hospitals to give eopportunity to the general practitioner to see typicalcases of the disease ; (2) it is doubtful if local authoritiesshould accept swabs for the diagnosis of acute throatconditions in children.

I am, Sir, yours faithfully,

July 3rd, 1923.DUNCAN FORBES,

Medical Officer of Health, Brighton.

R.A.M.C. MEMORIAL IN DUBLIN.-On July 4thSir John Goodwin, Director-General of the Army MedicalService, unveiled in St. Patrick’s Cathedral, Dublin, amemorial to the officers and men of the Royal Army MedicalCorps who fell in the late war. The memorial is a marbletablet, a replica of that erected some months ago in West-minster Abbey. There was a large attendance at theunveiling ceremony.