1089 To turn to another
point. Proximal ligation-of vessels chancy business. In this operation it may devascularise too much or too little of the lower pole, and so prove either dangerous or useless. Certainly with a wedge excision it cannot be easy to judge the extent of devascularisation. Is it not safer to ligate only such vessels is
always
a
divided when the excision reaches the hilum ? Admittedly the number of guillotine cases reported5 by me was small-10 in all-but I have added another 4 since, and now Murphy in a personal communication to Parry and Finelli 6 mentions a further 21 with satisfactory results. The total is still small, but may increase as time goes on. STEPHEN POWER. London, W.1.
These findings support the view that reactions 200 T.U. are specific. The M.R.C. is to be congratulated on restoring our faith in the value of the tuberculin test. A. C. PENMAN Cheshire Joint Sanatorium, D. H. ROXBURGH. Market Drayton, Salop. 25 years. 100 or
to
even
as are
PROPHYLAXIS IN THROMBOEMBOLISM
SIR,-In your leading article last week you were good enough to mention the paper by Dr. Gallagher and myself in the same issue of The Lancet. You referred to 2 cases of fatal haemorrhage in the series of patients given prophylaxis with phenindione. I am pleased to say that this is an error on your part, because there were no such cases. Presumably you meant to refer to the 2 cases of fatal pulmonary embolism which occurred after prophylaxis with phenindione had been stopped. In the trial, the absence of serious haemorrhagic complications was
noteworthy. May I comment
on another point ? You build a superstructure of argument on the hypothetical concept of a link between " trauma, thrombosis, and the tendency to sudden hxmorrhage ". In my opinion the concept is fallacious because the premise is untrue. Hxmorrhage after injury, massive or otherwise, has no connection with deep-vein thrombosis in the lower limbs. Bleeding after injury always has a local cause, although of course it can be more serious or extensive if there is an underlying haemorrhagic diathesis like haemophilia or scurvy. Bleeding into or from an injured area is due to torn bloodvessels ; whilst the occasional cases of melsena or hxmatemesis which usually occur days or weeks after trauma
(almost) always due to peptic ulceration, antedating complicating trauma. The danger of bleeding from peptic ulcers is of special importance in relationship to our proposal for prophylaxis with phenindione against venous thrombosis and pulmonary embolism; it requires special precautions, but that is another story. are or
Birmingham Accident Hospital.
SIMON SEVITT.
SPECIFIC TUBERCULIN REACTION were particularly interested to read your article of Nov. 14 on the investigation carried out leading the Medical Research Council into the specificity of by weak tuberculin reactions, as our own experience has been at variance with the opinions expressed by Palmer.’7
SIR,-We
Approximately 121/2% of new recruits to the staff of our sanatorium fail to react to 10 tuberculin units (T.u.) but react to 100 or 200 T.u. of P.P.D. These weak reactors do not develop primary tuberculosis, whereas in pre-B.c.G. days tuberculin-negative staff converted to positive after an average of 4-4 months, and about 10% of the convertors developed clinical primary tuberculosis. At this rate we should have had about 1 case of tuberculosis a year from the weak reactors. In fact there has been 1 case in 5. ibid. 1958, ii, 1257. 6. Parry, W. I., Finelli, J. F. J. Urol. 1959, 82, no. 5. 7. Palmer, C. E. Amer. Rev. Tuberc. 1953, 68, 678. 8. Edwards, P. W., Penman, A. C. Lancet, 1945, i, 429.
ORTHO-CRESYL PHOSPHATE POISONING
SIR,-The gravity of the mass outbreak of tri-orthocresyl-phosphate (T.O.C.P.) poisoning in Morocco must be our excuse for an intrusion into fields special to others; the outbreak has prompted us to put forward a hypothesis formulated during our study of an earlier outbreak.1 In T.O.C.P. poisoning, it is widely agreed that the essential lesion is demyelination of the peripheral nerves, the anterior roots, the columns of Goll, and the lower pyramidal tracts. Clinically, there is a delayed onset of motor paralysis of the limbs, with a slighter and transient sensory loss. T.o.c.P. belongs to the group of anticholinesterases and it is an irreversible cholinesterase inhibitor.
inhibition.-Experimentally, its main effect is depress pseudocholinesterase levels, while its effect on true cholinesterase is slight. The organic phosphorus compounds, ’Mipafox’ and possiblyParathion’, also produce a delayed paralysis and D.F.P. has produced a similar effect in chicks. Mipafox and parathion, however, depress both true cholinesterase and pseudocholinesterase levels, while D.F.P. depresses mainly true cholinesterase. Although the delayed motor paralysis of T.O.C.P. is very similar to that of mipafox, patients poisoned by mipafox suffer acute cholinergic effects immediately after ingestion of the poison. In T.o.c.P. poisoning the only possible equivalents are the inconstant and usually mild gastrointestinal upsets which are sometimes reported during the latent period. The symptoms of neuromuscular block which occur in mipafox poisoning, in particular fatigability, spasms and twitching with exercise,2 are not found in T.O.C.P. poisoning. Occasionally, patients in our series reported sudden falls immediately preceding the onset of paralysis (the patient falls and rises again two or three times, then walks again for some yards), a symptom which could be related to block, but this phenomenon was variable and short-lived. Symptoms which resemble nicotinelike cholinergic effects may, however, accompany T.O.C.P. poisoning. In our cases muscular cramps were always present at the time of onset and muscular fibrillation has been reported.33 But these symptoms do not occur at the time of ingestion when the cholinergic effects would be expected, but after a latent period at the time of onset. Cholinesterase
to
Thus in
poisoning the absence of the usual cholinergic symptoms at the time of ingestion of the poison, the fact that true cholinesterase levels are not depressed, the presence of sensory changes, and the distribution of demyelination in specific tracts make untenable any theory of simple anticholinesterase effects, such 4 as that suggested by Koelle and Gilman. T.O.C.P.
Pseudocholinesterase and demyelination.-The paralysis is probably directly related to demyelination. It has been suggested that antipseudocholinesterase activity might cause the demyelination,5 but Paton 6 points out that antipseudocholinesterases other than T.o.c.P., mipafox, and parathion do not cause demyelination, while with these three poisons the depression in pseudocholinesterase levels is not concurrent in time with the demyelination. In T.O.C.P. depressed pseudocholinesterase levels would be expected shortly after ingestion Susser, M. W., Stein, Z. Brit. J. industr. Med. 1957, 14, 111. Bidstrup, P. L., Bonnel, J. H., Beckett, A. G. Brit. med. J. 1953, i, 1068. Hunter, D., Perry, K. M. A., Evans, P. B. Brit. J. industr. Med. 1944, 1, 227. 4. Koelle, G. B., Gilman, A. J. Pharmacol. 1949, 95 (Pharm. Review, 166). 5. Earl, C. J., Thompson, R. H. S. Brit. J. Pharmacol. 1952, 7, 261. 6. Paton, W. D. M. in Lectures on the Scientific Basis of Medicine, 1953-54; p. 105. London, 1954.
1. 2. 3.