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ACTION OF HEPARIN IN ISCHÆMIC HEART-DISEASE
1405
nation-wide prophylactic therapy before the harmful effect due to relatively small doses was recognised.6I do not think it an unreasonable suggestion that if, as at present, several hypocholesterolaemic agents are available, those to be used in an attempt to prevent coronaryartery disease should not include any which might conceivably be harmful. It remains to be proved beyond reasonable doubt that cod-liver oil is completely harmless. Royal Hospital for Sick Children, Glasgow.
ERIC N. COLEMAN.
BIOCHEMICAL INDIVIDUALITY SIR,-Your leading article of March 25 called attentior to an important field, but did not do it justice. The whole problem of innate resistance or susceptibility to man3 metabolic as well as infectious diseases is coming to the fore, and is based upon biochemical individuality (as wel as individuality in other fields). If members of the human family were assembly-line product: -all alike-there would be no such thing as innate resistance or susceptibility. My book, Biochemical Individuality (1956); is the only one which treats this subjects as well as some related material on anatomical and physiological individuality. The idea of biochemical individuality is crucial to the genetotrophic concept of disease which was first set forth in The Lancet ir. 1950.’ Department of Chemistry, University of Texas, Austin, Texas.
ROGER
industrialisation, with its improved communications and accelerated drift of the rural population to the towns, tends to perpetuate the vicious cycle of infection and disease. Obviously this situation can only be effectively dealt with by extensive and well-planned measures directed towards detecting and treating the infectious patient-and these will take time, effort, and money. Meanwhile, this country could make an indirect contribution by undertaking an intensive study, by X-ray and tuberculin testing, of the Indian and Pakistani communities resident here. A good deal of information is already available; but perhaps this could be coordinated and the methods of effectively controlling the situation more thoroughly elucidated. Clare Hall Hospital, South Mimms, Barnet.
J. WILLIAMS.
MEDIASTINAL LYMPHATIC GLAND TUBERCULOSIS IN IMMIGRANTS SiR,-Like Dr. Silver and Dr. Steel (June 10) we have observed mediastinal lymph-node tuberculosis in coloured immigrants, and also in a young man of Welsh parentage; other cases have been reported from this hospital in both British-born and Asian patients.8 We would agree, however, that the condition occurs more commonly amongst Indians and West Indians, and that it is associated with low resistance to tuberculosis; in patients with this type of lesion miliary tuberculosis and other extrapulmonary foci sometimes develop. The most immediate danger, however, is rupture of the caseous lymph-node into a main bronchus; and thoracotomy may
be urgently indicated. Most of our patients with this lesion appear to have come from villages or farms in India or one of the smaller West Indian islands. In both cases former generations would have been relatively isolated from infection, with the result that many are still unduly susceptible and infection is rapidly followed by disease. It is because their inherited resistance is poor that their response is inadequate to deal with the primary infection, with resultant massive caseation of lymph-nodes and other severe manifestations of uncontrolled disease.9 Indian villages, even in the plains, have still little with the outside world, and when their inhabitants migrate to a city, be it Bombay, Karachi, or London, many will be meeting infection for the first time. Roe,1O for example, found in an Indian community at Uxbridge that 29 (66%) out of 44 were Mantoux-negative (1:1000 o.T.), they were mainly Sikhs from farming communities. On the other hand we also find here Indian and Pakistani patients with old-standing cavitary lesions, some of whom arrive in this state Inevitably,
Many
contact
5. 6. 7. 8. 9.
the two groups intermingle, usually under adverse conditions, in the older and more congested parts of our larger cities. The results of this explosive combination are seen in the form of grossly enlarged lymph-nodes, acute pleural effusions, and rapidly progressive pulmonary disease, as described by Stevenson 12 in Bradford. We would appear to be encountering in this country in small degree what is happening continuously and on a massive scale in India, Pakistan, and other countries where tuberculosis is still rife, and where the progress of
Butler, N. R. Proc. R. Soc. Med. 1951, 44, 296. Lightwood, R. ibid. 1952, 45, 401. Williams, R. J., Beerstecher, E., Berry, L. J. Lancet, 1950, i, 287. Harvey-Samuel, R. E. D. Tubercle, 1955, 37, 255. Cummins, L. Primitive Tuberculosis. London, 1959. 10. Roe, J. T. N. Tubercle, 1959, 40, 387. 11. Springett, V. H., Adams, J. C., D’Costa, T. B., Hemming, M. Brit. J. prev. soc. Med. 1958, 12, 135.
NORMAN MACDONALD H. L. KHANCHANDANI.
ACTION OF HEPARIN IN ISCHÆMIC HEART-DISEASE
SIR,-In his letter (May 13) Dr. Poller points out that has thrombogenic properties by virtue of an antiheparin action or by directly causing thrombosis.13He indicates that both the antiheparin activity and thrombusinducing activity of sera can be removed by absorption with aluminium hydroxide, and that this activity is present in the serum of patients with factor-vn deficiency, severe phenindione-induced deficiencies, and severe Christmas-factor deficiency. Although this activity is decreased in the third condition, it could still be serum
demonstrated. I think it worth recalling that serum has at least one other property in relation to thrombosis-its power to induce platelet clumping or " viscous metamorphosis " (v.M.) in washed suspensions of platelets. This property was described by Wright and Minotl4; and I have attempted to define the properties of this platelet-v.M. factor of serum." This factor could be absorbed on to aluminium hydroxide or barium sulphate, and was present in fresh serum derived from blood deficient in antihasmophilic globulin, Christmas factor, factors v and VII, plasma-thromboplastin antecedent, and platelets. In addition it was present in patients who had von Willebrand’s syndrome. It was partially destroyed by heat, was stable on storage at room temperature, and required calcium for its action. Heparin neutralised or destroyed the factor completely. It has been claimed that this serum factor is in fact thrombin16; but human thrombin will not clump washed suspensions of human platelets, and sera which are capable of inducing platelet clumping cannot convert fibrinogen to fibrin. The factor could be absorbed from serum by washed platelets. These results do not identify the factor or factors responsible; but they do suggest that Wessler’s thrombogenic serum factor might act by producing platelet clumping and so encouraging fibrin formation. It is impossible to connect the plateletclumping activity with the antiheparin effect, but the association may be of considerable importance. 12. Stevenson, D. K. Tubercle, 1959, 40, 491. 13. Wessler, S., Reimer, S. M. J. clin. Invest. 1960, 39, 262. 14. Wright, H. J., Minot, G. R. J. exp. Med. 1917, 26, 395. 15. Sharp, A. A. Thesis for the Degree of Doctor of Medicine, 16.
University, 1957. Stefanini, M., Silverberg, J.
H. Amer.
Edinburgh
J. clin. Path. 1951, 21,
1030.
1406
Whatever the explanation, these results do suggest that these three activities of serum may be caused by one factor, a factor that is probably distinct from any known coagulation factor. The Radcliffe Infirmary, Oxford.
A. A. SHARP.
RUPTURE OF THE POSTERIOR URETHRA
SIR,-Ishould like to suggest that the fundamental principles of wound treatment, correctly emphasised by Mr. Wilkinson (May 27), are not being fully carried out if the urethral wound is being irritated by urine or by an indwelling catheter, whether a Foley or a plastic one as recommended by Mr. Scorer (June 10). I consider that better-almost ideal-conditions for primary healing are obtained by immediate primary suture, not using a urethral catheter, and nursing in high Trendelenburg posture with suprapubic bladder drainage. By this method the urethra is kept completely dry and non-irritated while healing occurs. A boy, aged 11, with fracture of the pelvis and complete rupture of the posterior urethra was treated by this method at Willesden General Hospital in 1958; through a perineal incision two hours after injury the wide separation between prostatic and membranous urethra: was overcome quite easily and primary suture performed. The bladder was drained by suprapubic catheter only, and high Trendelenburg posture was strictly maintained for two weeks. The suprapubic catheter was taken out a few days later. Micturition was normal within a few days, and there was only very slight urinary infection. Three years later there are no symptoms. No catheters dilators have been passed since the initial operation.
or
I believe that immediate clean primary healing occurred because of the complete absence of irritation of the urethral wound by urine or catheter for two weeks. Unfortunately I have not yet had the opportunity of treating another such case-perhaps owing to the highly organised disposal of such injuries to the proper units!i London, W.1.
GEORGE
QVIST.
SIR,-Mr. Scorer (June 10) says that the traction method of treatment using a Foley catheter is difficult or impossible to apply to the ruptured urethra in boys owing to the small size of the urethra. He is to be congratulated on the good results he obtained by a non-traction method; but I believe, nevertheless, that traction is the only technique which will certainly maintain the urethral ends in accurate apposition and thus avoid the often irreparable complications of stricture, fistulse, and incontinence which may be the sequel of simply leaving a catheter across the gap. Traction is suitable for any age; the accompanying figure illustrates a technique which I used successfully in a
boy aged 4 1/2 years.
A 14 F de Pezzer catheter was brought
through a perineal urethrostomy. The prostate
was
cor-
rectly positioned against the perineal membrane by pulling on the catheter
before the bladder and abdominal wounds were closed. Whilst pull was maintained, adhesive strapping, 1 in. wide, was wrapped around the catheter to produce a firm mass close to the perineal skin; the catheter was transfixed with a safety-pin just below the mass to prevent it slipping. The bladder was drained above the pubis, and a thread attached to the’expanded end of the de Pezzer catheter was brought through the wound beside the suprapubic catheter. When the child returned to bed, weight traction was applied to the perineal catheter. This catheter was removed after two weeks, and the suprapubic catheter two weeks later. For three months the child had incomplete control, but he has been fully continent since. Instrumentation has never revealed any narrowing of the urethra; and intravenous pyelography and urinalysis are
the
normal.
A perineal rather than a penile catheter has several advantages. A larger and stronger catheter may be used; there is no risk of stricture formation in the penile urethra; traction can be applied in an axis corresponding to that of the prostatic urethra; and, not least important, it is much more comfortable. The mass of adhesive strapping on the catheter is an essential factor in maintaining the ruptured urethral ends constantly in contact, since they are compressed between it and the expanded end of the catheter. With traction alone there is always the possibility of displacement of the proximal urethra if the pull is temporarily relaxed-as it often is, during movement of the patient in bed. For my patient I chose a de Pezzer catheter because
I was uncertain whether the balloon of a Foley catheter would tolerate traction for a long time. From Mr. Wilkinson’s experience it obviously does, and a Foley catheter is probably preferable for the purpose. Incidentally, the smallest Foley catheter obtainable is size 10 F, and not 12 F as suggested by Mr. Scorer. Alder
Hey Children’s Hospital, Liverpool, 12.
J. H. JOHNSTON.
TREATMENT OF LICHEN PLANUS
SIR,-In your annotation (June 10) you mention .’ Dipasic ’ as a drug which has produced good results in the hands of Dr. Alexander,! and say that further trials with this drug are required. Unfortunately, Dr. Alexander overlooked the natural history of lichen planus. Many cases clear spontaneously in 6-9 months from the time when symptoms begin. Many patients with lichen planus do not see a dermatologist for three" months or longer; and if a further three months’ treatment is added to this, the patient may well reach the period of spontaneous resolution. If dipasic was of value in treatment it seemed to me to be an important advance; so I immediately tried to reproduce Dr. Alexander’s results. In a double-blind trial with dummy tablets, I have had the following results to date after three months’ treatment": "
"
patients given dipasic took the tablets for one month only; they had not improved they did not return for observation until sent for. After three months 1 had improved and the other was much worse. These 2 are not included in the figures given above. An additional 12 patients were given dipasic uncontrolled, either because they were seen before I had access to dummy tablets or because they were seen at hospitals where I did not have a supply of dummy tablets. 4 of these patients might be ’
2
as
described
difficult because the disease had been present a of these 4 was improved. The results in the long time; other 8 after three months were: as
none
1. Alexander, J. O’D. Brit. J. Derm.
1960, 72, 355.
nation-wide prophylactic therapy before the harmful effect due to relatively small doses was recognised.6I do not think it an unreasonable suggestion that if, as at present, several hypocholesterolaemic agents are available, those to be used in an attempt to prevent coronaryartery disease should not include any which might conceivably be harmful. It remains to be proved beyond reasonable doubt that cod-liver oil is completely harmless. Royal Hospital for Sick Children, Glasgow.
ERIC N. COLEMAN.
BIOCHEMICAL INDIVIDUALITY SIR,-Your leading article of March 25 called attentior to an important field, but did not do it justice. The whole problem of innate resistance or susceptibility to man3 metabolic as well as infectious diseases is coming to the fore, and is based upon biochemical individuality (as wel as individuality in other fields). If members of the human family were assembly-line product: -all alike-there would be no such thing as innate resistance or susceptibility. My book, Biochemical Individuality (1956); is the only one which treats this subjects as well as some related material on anatomical and physiological individuality. The idea of biochemical individuality is crucial to the genetotrophic concept of disease which was first set forth in The Lancet ir. 1950.’ Department of Chemistry, University of Texas, Austin, Texas.
ROGER
industrialisation, with its improved communications and accelerated drift of the rural population to the towns, tends to perpetuate the vicious cycle of infection and disease. Obviously this situation can only be effectively dealt with by extensive and well-planned measures directed towards detecting and treating the infectious patient-and these will take time, effort, and money. Meanwhile, this country could make an indirect contribution by undertaking an intensive study, by X-ray and tuberculin testing, of the Indian and Pakistani communities resident here. A good deal of information is already available; but perhaps this could be coordinated and the methods of effectively controlling the situation more thoroughly elucidated. Clare Hall Hospital, South Mimms, Barnet.
J. WILLIAMS.
MEDIASTINAL LYMPHATIC GLAND TUBERCULOSIS IN IMMIGRANTS SiR,-Like Dr. Silver and Dr. Steel (June 10) we have observed mediastinal lymph-node tuberculosis in coloured immigrants, and also in a young man of Welsh parentage; other cases have been reported from this hospital in both British-born and Asian patients.8 We would agree, however, that the condition occurs more commonly amongst Indians and West Indians, and that it is associated with low resistance to tuberculosis; in patients with this type of lesion miliary tuberculosis and other extrapulmonary foci sometimes develop. The most immediate danger, however, is rupture of the caseous lymph-node into a main bronchus; and thoracotomy may
be urgently indicated. Most of our patients with this lesion appear to have come from villages or farms in India or one of the smaller West Indian islands. In both cases former generations would have been relatively isolated from infection, with the result that many are still unduly susceptible and infection is rapidly followed by disease. It is because their inherited resistance is poor that their response is inadequate to deal with the primary infection, with resultant massive caseation of lymph-nodes and other severe manifestations of uncontrolled disease.9 Indian villages, even in the plains, have still little with the outside world, and when their inhabitants migrate to a city, be it Bombay, Karachi, or London, many will be meeting infection for the first time. Roe,1O for example, found in an Indian community at Uxbridge that 29 (66%) out of 44 were Mantoux-negative (1:1000 o.T.), they were mainly Sikhs from farming communities. On the other hand we also find here Indian and Pakistani patients with old-standing cavitary lesions, some of whom arrive in this state Inevitably,
Many
contact
5. 6. 7. 8. 9.
the two groups intermingle, usually under adverse conditions, in the older and more congested parts of our larger cities. The results of this explosive combination are seen in the form of grossly enlarged lymph-nodes, acute pleural effusions, and rapidly progressive pulmonary disease, as described by Stevenson 12 in Bradford. We would appear to be encountering in this country in small degree what is happening continuously and on a massive scale in India, Pakistan, and other countries where tuberculosis is still rife, and where the progress of
Butler, N. R. Proc. R. Soc. Med. 1951, 44, 296. Lightwood, R. ibid. 1952, 45, 401. Williams, R. J., Beerstecher, E., Berry, L. J. Lancet, 1950, i, 287. Harvey-Samuel, R. E. D. Tubercle, 1955, 37, 255. Cummins, L. Primitive Tuberculosis. London, 1959. 10. Roe, J. T. N. Tubercle, 1959, 40, 387. 11. Springett, V. H., Adams, J. C., D’Costa, T. B., Hemming, M. Brit. J. prev. soc. Med. 1958, 12, 135.
NORMAN MACDONALD H. L. KHANCHANDANI.
ACTION OF HEPARIN IN ISCHÆMIC HEART-DISEASE
SIR,-In his letter (May 13) Dr. Poller points out that has thrombogenic properties by virtue of an antiheparin action or by directly causing thrombosis.13He indicates that both the antiheparin activity and thrombusinducing activity of sera can be removed by absorption with aluminium hydroxide, and that this activity is present in the serum of patients with factor-vn deficiency, severe phenindione-induced deficiencies, and severe Christmas-factor deficiency. Although this activity is decreased in the third condition, it could still be serum
demonstrated. I think it worth recalling that serum has at least one other property in relation to thrombosis-its power to induce platelet clumping or " viscous metamorphosis " (v.M.) in washed suspensions of platelets. This property was described by Wright and Minotl4; and I have attempted to define the properties of this platelet-v.M. factor of serum." This factor could be absorbed on to aluminium hydroxide or barium sulphate, and was present in fresh serum derived from blood deficient in antihasmophilic globulin, Christmas factor, factors v and VII, plasma-thromboplastin antecedent, and platelets. In addition it was present in patients who had von Willebrand’s syndrome. It was partially destroyed by heat, was stable on storage at room temperature, and required calcium for its action. Heparin neutralised or destroyed the factor completely. It has been claimed that this serum factor is in fact thrombin16; but human thrombin will not clump washed suspensions of human platelets, and sera which are capable of inducing platelet clumping cannot convert fibrinogen to fibrin. The factor could be absorbed from serum by washed platelets. These results do not identify the factor or factors responsible; but they do suggest that Wessler’s thrombogenic serum factor might act by producing platelet clumping and so encouraging fibrin formation. It is impossible to connect the plateletclumping activity with the antiheparin effect, but the association may be of considerable importance. 12. Stevenson, D. K. Tubercle, 1959, 40, 491. 13. Wessler, S., Reimer, S. M. J. clin. Invest. 1960, 39, 262. 14. Wright, H. J., Minot, G. R. J. exp. Med. 1917, 26, 395. 15. Sharp, A. A. Thesis for the Degree of Doctor of Medicine, 16.
University, 1957. Stefanini, M., Silverberg, J.
H. Amer.
Edinburgh
J. clin. Path. 1951, 21,
1030.
1406
Whatever the explanation, these results do suggest that these three activities of serum may be caused by one factor, a factor that is probably distinct from any known coagulation factor. The Radcliffe Infirmary, Oxford.
A. A. SHARP.
RUPTURE OF THE POSTERIOR URETHRA
SIR,-Ishould like to suggest that the fundamental principles of wound treatment, correctly emphasised by Mr. Wilkinson (May 27), are not being fully carried out if the urethral wound is being irritated by urine or by an indwelling catheter, whether a Foley or a plastic one as recommended by Mr. Scorer (June 10). I consider that better-almost ideal-conditions for primary healing are obtained by immediate primary suture, not using a urethral catheter, and nursing in high Trendelenburg posture with suprapubic bladder drainage. By this method the urethra is kept completely dry and non-irritated while healing occurs. A boy, aged 11, with fracture of the pelvis and complete rupture of the posterior urethra was treated by this method at Willesden General Hospital in 1958; through a perineal incision two hours after injury the wide separation between prostatic and membranous urethra: was overcome quite easily and primary suture performed. The bladder was drained by suprapubic catheter only, and high Trendelenburg posture was strictly maintained for two weeks. The suprapubic catheter was taken out a few days later. Micturition was normal within a few days, and there was only very slight urinary infection. Three years later there are no symptoms. No catheters dilators have been passed since the initial operation.
or
I believe that immediate clean primary healing occurred because of the complete absence of irritation of the urethral wound by urine or catheter for two weeks. Unfortunately I have not yet had the opportunity of treating another such case-perhaps owing to the highly organised disposal of such injuries to the proper units!i London, W.1.
GEORGE
QVIST.
SIR,-Mr. Scorer (June 10) says that the traction method of treatment using a Foley catheter is difficult or impossible to apply to the ruptured urethra in boys owing to the small size of the urethra. He is to be congratulated on the good results he obtained by a non-traction method; but I believe, nevertheless, that traction is the only technique which will certainly maintain the urethral ends in accurate apposition and thus avoid the often irreparable complications of stricture, fistulse, and incontinence which may be the sequel of simply leaving a catheter across the gap. Traction is suitable for any age; the accompanying figure illustrates a technique which I used successfully in a
boy aged 4 1/2 years.
A 14 F de Pezzer catheter was brought
through a perineal urethrostomy. The prostate
was
cor-
rectly positioned against the perineal membrane by pulling on the catheter
before the bladder and abdominal wounds were closed. Whilst pull was maintained, adhesive strapping, 1 in. wide, was wrapped around the catheter to produce a firm mass close to the perineal skin; the catheter was transfixed with a safety-pin just below the mass to prevent it slipping. The bladder was drained above the pubis, and a thread attached to the’expanded end of the de Pezzer catheter was brought through the wound beside the suprapubic catheter. When the child returned to bed, weight traction was applied to the perineal catheter. This catheter was removed after two weeks, and the suprapubic catheter two weeks later. For three months the child had incomplete control, but he has been fully continent since. Instrumentation has never revealed any narrowing of the urethra; and intravenous pyelography and urinalysis are
the
normal.
A perineal rather than a penile catheter has several advantages. A larger and stronger catheter may be used; there is no risk of stricture formation in the penile urethra; traction can be applied in an axis corresponding to that of the prostatic urethra; and, not least important, it is much more comfortable. The mass of adhesive strapping on the catheter is an essential factor in maintaining the ruptured urethral ends constantly in contact, since they are compressed between it and the expanded end of the catheter. With traction alone there is always the possibility of displacement of the proximal urethra if the pull is temporarily relaxed-as it often is, during movement of the patient in bed. For my patient I chose a de Pezzer catheter because
I was uncertain whether the balloon of a Foley catheter would tolerate traction for a long time. From Mr. Wilkinson’s experience it obviously does, and a Foley catheter is probably preferable for the purpose. Incidentally, the smallest Foley catheter obtainable is size 10 F, and not 12 F as suggested by Mr. Scorer. Alder
Hey Children’s Hospital, Liverpool, 12.
J. H. JOHNSTON.
TREATMENT OF LICHEN PLANUS
SIR,-In your annotation (June 10) you mention .’ Dipasic ’ as a drug which has produced good results in the hands of Dr. Alexander,! and say that further trials with this drug are required. Unfortunately, Dr. Alexander overlooked the natural history of lichen planus. Many cases clear spontaneously in 6-9 months from the time when symptoms begin. Many patients with lichen planus do not see a dermatologist for three" months or longer; and if a further three months’ treatment is added to this, the patient may well reach the period of spontaneous resolution. If dipasic was of value in treatment it seemed to me to be an important advance; so I immediately tried to reproduce Dr. Alexander’s results. In a double-blind trial with dummy tablets, I have had the following results to date after three months’ treatment": "
"
patients given dipasic took the tablets for one month only; they had not improved they did not return for observation until sent for. After three months 1 had improved and the other was much worse. These 2 are not included in the figures given above. An additional 12 patients were given dipasic uncontrolled, either because they were seen before I had access to dummy tablets or because they were seen at hospitals where I did not have a supply of dummy tablets. 4 of these patients might be ’
2
as
described
difficult because the disease had been present a of these 4 was improved. The results in the long time; other 8 after three months were: as
none
1. Alexander, J. O’D. Brit. J. Derm.
1960, 72, 355.