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DEFIBRINATION SYNDROME
232 time 31-34 seconds, control 14 seconds, by Wollenweber’s modified Quick test), while the second had a fall of haemoglobin from 14 to 7 g. per 100 ml. before bleeding ceased (prothrombin-time 30 seconds, control 15 seconds). It should be borne in mind that blood-loss from oral surgery is often comparable with that of major surgery; Johnson 18 gives an average value of 200 ml.—on occasions this is much more, a point of some importance in severe ischsemic heart-disease. Askey and Cherry 19 performed 14 extractions in 6 patients with one mild hemorrhage. Behrman and Wright 20 give details of the regimen to avoid " swinging " of the prothrombin-time, and pay particular attention to careful surgical technique. Spouge,21 as Dr. McIntyre mentioned, allows the prothrombin-time to rise to 50% of normal for 48 hours. Tulloch and Wright 22 described 15 extractions in 14 patients; they stopped anticoagulants 4 days before surgery. An editorial article in the New England Journal of Medicine condemned dental surgery during anticoagulant therapy.23 In this centre, precautions are taken not to alter the haemostatic status of these patients suddenly, and we are unaware of untoward haemorrhage. It is clear that as Dr. McIntyre states " Opinions differ as to management "; a carefully controlled survey of this problem would be most helpful. Finally the dose of penicillin advised for patients with rheumatic heart-disease would be considered inadequate in this hospital. Department of Clinical Pathology Queen Elizabeth Hospital, J. J. TAYLOR. Birmingham 15.
DEFIBRINATION SYNDROME have read with interest the comments of Dr. Clarke SIR,—I and Margaret Collins (July 2). Their reference to " the immediate thrombotic effect of endothelial cell injury by pinching 24 or laser beam 25" is misleading for the following reasons:
1. The effect of pinching is described by Honour and Ross Russell24 thus: "Pinching the artery gently between the ends of a pair of needle forceps so that no bleeding occurred was almost always ineffective, although local contraction was frequent. Repeated applications of gentle pinching in the same spot occasionally produced a small number of thrombi which embolized before reaching a size large enough to block the vessel." This is undoubtedly different from the implications of the statement by Dr. Clarke and Margaret Collins. 2. Thermal injury as well as repeated pinching produces white thrombi which were found by electron microscopy 24 to be composed of platelets packed tightly together-a result most probably produced by platelet adhesion and aggregation rather than by thromboplastin. Furthermore, it is common knowledge that heat (even as low as 60°C) denatures proteins and coagulates fibrinogen. 3. My work 21 is concerned with the gradual production in tissues of full thromboplastic activity as a result of an interaction between the clotting factors (VIII, ix, and platelet-like) therein, while Dr. Clarke’s investigations 27 deal with the final thromboplastic product in homogenised tissues. The formation of tissue thromboplastin is a time-consuming process, although the rate of achieving full activity varies in different organs.2B
I would also add that the condition of being histologically intact is no indication of the state of the clotting factors in tissues. In my opinion, as far as clotting factors in blood and tissues are concerned, any change in their environment, whether physical, chemical, or thermal, is traumatic; their mere removal outside the body is injurioUS,211 altering their in-vivo properties. Department of Pathology,
Shenley Hospital, Hertfordshire.
F. NOUR-ELDIN.
Johnson, R. L. J. dent. Res. 1956, 35, 175. Askey, J. M., Cherry, C. B. Calif. Med. 1956, 84, 16. Behrman, S. J., Wright, I. S. J. Am. med. Ass. 1961, 175, 483. Spouge, J. D. Oral Surg. 1964, 18, 70. Tulloch, J. Wright, I. S. Circulation, 1954, 9, 823. New Engl. J. Med. 1957, 256, 367. Honour, A. J., Ross Russell, R. W. Br. J. exp. Path. 1962, 43, 350. Grant, L., Becker, F. Archs Path. 1966, 81, 36. 26. Nour-Eldin, F. Ann. N. Y. Acad. Sci. (in the press). 27. Clarke, N. Nature, Lond. 1965, 205, 608. 28. Nour-Eldin, F. Ann. N.Y. Acad. Sci. 1964, 105, 983. 18. 19. 20. 21. 22. 23. 24. 25.
MITOGENIC ACTION OF TRYPSIN AND CHYMOTRYPSIN been investigating the mitogenic action of have SIR,-We antigens on in-vitro short-term cultures of human lymphocytes, Lately we have seen a woman who had had severe allergic shock after parenteral administration of an anti-inflammatory product containing trypsin and chymotrypsin (’ Paratripsin composto’, Istituto Sieroterapico Milanese). We found that this product had a mitogenic action in vitro on the lymphocytes from the patient; surprisingly enough, it also stimulated mitogenic action in control cultures of lymphocytes from two normal subjects, and we wondered if it had a non-specific action on lympho. cytes independent of its antigenic properties. The experiment was repeated on six cultures of lymphocytes from six normal subjects. In all cases blastic transformation occurred, though with variable intensity: at the 96th hour blastic elements ranged from 2% to 14% of cultured cells. Since the product consists of two different enzymes, the mitogenic action of each enzyme was tested separately on cultures from three normal subjects and found to be almost identical in intensity. There were no structural differences between the blasts produced in all these experiments and the blasts activated by phytohasmagglutinin P(Difco) in control cultures of the same
lymphocytes.
These preliminary results (a) point to the existence of new substances with mitogenic action on human peripheral-blood lymphocytes and (b) contribute to the clarification of the mechanism by which phytohaemagglutinin (P.H.A.) initiates structural changes in lymphocytes. It is still under discussion whether the mitogenic action of P.H.A. is due to a generic surface action-namely, an " irritative condition " related to the well-known tropism of P.H.A. for cell membrane.! On the other hand, since the effects of P.H.A. on lymphocyte cultures are similar to the effects of in-vitro exposure to antigen on lymphocytes from specifically sensitised subjects, the mitogenic action of P.H.A. may be the equivalent of an immune or paraimmune reaction.23 Since trypsin and chymotrypsin are both substances which act on a cell suspension by damaging the cell surface, our observations support the hypothesis that the mitogenic action on lymphocytes of P.H.A./ serum from rabbits immunised with a human leucocyte concentrate,4 filtrate of staphylococcal cultures5 and staphylococcal hxmolysins6 may also result from an analogous mechanism, unrelated to specific antigenic functions. DOMENICO MAZZEI CARLO NOVI Institute of Medical Pathology CLAUDIO BAZZI. Milan University, Italy.
POSTOPERATIVE INFECTION IN AN EYE HOSPITAL
SIR,-In view of the article by Dr. Ayliffe and his colleagues7 and the letters from Professor Norton8 and Mr. Baker and his co-authors,9 we express these opinions: The production of eye-drops, whether by commercial firms; or by hospital or retail pharmacists, must be a compromise between the theoretical and the practical standards. The one essential principle is that all ophthalmic solutions are sterile, and this is best achieved by autoclaving. An effective bactericide, especially against Pseudomonas pyocyanea (Ps. aeruginosa), must be included except for intracameral use. Some decomposition of drugs will occur during autoclaving, Nowell, P. C. Cancer Res. 1960, 20, 462. Pearmain, G., Lycette, R. R., Fitzgerald, P. H. Lancet, 1963, i, 637. Elves, M. W., Roath, S., Israëls, M. C. G. ibid. p. 806. Grãsbeck, R., Nordman, C., de la Chapelle, A. ibid. 1963, ii, 385. Ling, N. R., Husband, E. M. ibid. 1964, i, 363. Ling, N. R., Spicer, E., James, K., Williamson, N. Br. J. Hœmat. 1965. 11, 421. 7. Ayliffe, G. A. J., Barry, D. R., Lowbury, E. J. L., Roper-Hall, M. J. Walker, W. M. Lancet, 1966, i, 1113. 8. Norton, D. A. ibid. p. 1422. 9. Baker, J. E. H., Furber, T. H., Leach, R. H., Steane, M. A. ibid. 1966. ii, 55.
1. 2. 3. 4. 5. 6.
DEFIBRINATION SYNDROME have read with interest the comments of Dr. Clarke SIR,—I and Margaret Collins (July 2). Their reference to " the immediate thrombotic effect of endothelial cell injury by pinching 24 or laser beam 25" is misleading for the following reasons:
1. The effect of pinching is described by Honour and Ross Russell24 thus: "Pinching the artery gently between the ends of a pair of needle forceps so that no bleeding occurred was almost always ineffective, although local contraction was frequent. Repeated applications of gentle pinching in the same spot occasionally produced a small number of thrombi which embolized before reaching a size large enough to block the vessel." This is undoubtedly different from the implications of the statement by Dr. Clarke and Margaret Collins. 2. Thermal injury as well as repeated pinching produces white thrombi which were found by electron microscopy 24 to be composed of platelets packed tightly together-a result most probably produced by platelet adhesion and aggregation rather than by thromboplastin. Furthermore, it is common knowledge that heat (even as low as 60°C) denatures proteins and coagulates fibrinogen. 3. My work 21 is concerned with the gradual production in tissues of full thromboplastic activity as a result of an interaction between the clotting factors (VIII, ix, and platelet-like) therein, while Dr. Clarke’s investigations 27 deal with the final thromboplastic product in homogenised tissues. The formation of tissue thromboplastin is a time-consuming process, although the rate of achieving full activity varies in different organs.2B
I would also add that the condition of being histologically intact is no indication of the state of the clotting factors in tissues. In my opinion, as far as clotting factors in blood and tissues are concerned, any change in their environment, whether physical, chemical, or thermal, is traumatic; their mere removal outside the body is injurioUS,211 altering their in-vivo properties. Department of Pathology,
Shenley Hospital, Hertfordshire.
F. NOUR-ELDIN.
Johnson, R. L. J. dent. Res. 1956, 35, 175. Askey, J. M., Cherry, C. B. Calif. Med. 1956, 84, 16. Behrman, S. J., Wright, I. S. J. Am. med. Ass. 1961, 175, 483. Spouge, J. D. Oral Surg. 1964, 18, 70. Tulloch, J. Wright, I. S. Circulation, 1954, 9, 823. New Engl. J. Med. 1957, 256, 367. Honour, A. J., Ross Russell, R. W. Br. J. exp. Path. 1962, 43, 350. Grant, L., Becker, F. Archs Path. 1966, 81, 36. 26. Nour-Eldin, F. Ann. N. Y. Acad. Sci. (in the press). 27. Clarke, N. Nature, Lond. 1965, 205, 608. 28. Nour-Eldin, F. Ann. N.Y. Acad. Sci. 1964, 105, 983. 18. 19. 20. 21. 22. 23. 24. 25.
MITOGENIC ACTION OF TRYPSIN AND CHYMOTRYPSIN been investigating the mitogenic action of have SIR,-We antigens on in-vitro short-term cultures of human lymphocytes, Lately we have seen a woman who had had severe allergic shock after parenteral administration of an anti-inflammatory product containing trypsin and chymotrypsin (’ Paratripsin composto’, Istituto Sieroterapico Milanese). We found that this product had a mitogenic action in vitro on the lymphocytes from the patient; surprisingly enough, it also stimulated mitogenic action in control cultures of lymphocytes from two normal subjects, and we wondered if it had a non-specific action on lympho. cytes independent of its antigenic properties. The experiment was repeated on six cultures of lymphocytes from six normal subjects. In all cases blastic transformation occurred, though with variable intensity: at the 96th hour blastic elements ranged from 2% to 14% of cultured cells. Since the product consists of two different enzymes, the mitogenic action of each enzyme was tested separately on cultures from three normal subjects and found to be almost identical in intensity. There were no structural differences between the blasts produced in all these experiments and the blasts activated by phytohasmagglutinin P(Difco) in control cultures of the same
lymphocytes.
These preliminary results (a) point to the existence of new substances with mitogenic action on human peripheral-blood lymphocytes and (b) contribute to the clarification of the mechanism by which phytohaemagglutinin (P.H.A.) initiates structural changes in lymphocytes. It is still under discussion whether the mitogenic action of P.H.A. is due to a generic surface action-namely, an " irritative condition " related to the well-known tropism of P.H.A. for cell membrane.! On the other hand, since the effects of P.H.A. on lymphocyte cultures are similar to the effects of in-vitro exposure to antigen on lymphocytes from specifically sensitised subjects, the mitogenic action of P.H.A. may be the equivalent of an immune or paraimmune reaction.23 Since trypsin and chymotrypsin are both substances which act on a cell suspension by damaging the cell surface, our observations support the hypothesis that the mitogenic action on lymphocytes of P.H.A./ serum from rabbits immunised with a human leucocyte concentrate,4 filtrate of staphylococcal cultures5 and staphylococcal hxmolysins6 may also result from an analogous mechanism, unrelated to specific antigenic functions. DOMENICO MAZZEI CARLO NOVI Institute of Medical Pathology CLAUDIO BAZZI. Milan University, Italy.
POSTOPERATIVE INFECTION IN AN EYE HOSPITAL
SIR,-In view of the article by Dr. Ayliffe and his colleagues7 and the letters from Professor Norton8 and Mr. Baker and his co-authors,9 we express these opinions: The production of eye-drops, whether by commercial firms; or by hospital or retail pharmacists, must be a compromise between the theoretical and the practical standards. The one essential principle is that all ophthalmic solutions are sterile, and this is best achieved by autoclaving. An effective bactericide, especially against Pseudomonas pyocyanea (Ps. aeruginosa), must be included except for intracameral use. Some decomposition of drugs will occur during autoclaving, Nowell, P. C. Cancer Res. 1960, 20, 462. Pearmain, G., Lycette, R. R., Fitzgerald, P. H. Lancet, 1963, i, 637. Elves, M. W., Roath, S., Israëls, M. C. G. ibid. p. 806. Grãsbeck, R., Nordman, C., de la Chapelle, A. ibid. 1963, ii, 385. Ling, N. R., Husband, E. M. ibid. 1964, i, 363. Ling, N. R., Spicer, E., James, K., Williamson, N. Br. J. Hœmat. 1965. 11, 421. 7. Ayliffe, G. A. J., Barry, D. R., Lowbury, E. J. L., Roper-Hall, M. J. Walker, W. M. Lancet, 1966, i, 1113. 8. Norton, D. A. ibid. p. 1422. 9. Baker, J. E. H., Furber, T. H., Leach, R. H., Steane, M. A. ibid. 1966. ii, 55.
1. 2. 3. 4. 5. 6.