- Email: [email protected]
SKIN FRAGMENTS REMOVED BY INJECTION NEEDLES
52 The very low incidence of hydramnios in cases of severe pre-eclampsia (approximately 14 in 1200 cases of severe pre-eclampsia) shows that undue distension of the uterus is not a cause of pre-eclampsia. A striking fact is that pre-eclampsia is particularly uncommon in severe hydramnios which is characteristic of those cases where the foetus has a gross malformation of the central nervous system. It appears that if hydramnios and severe pre-eclampsia occur together some unknown factor causes both conditions. Midwifery Department, IAN MACGILLIVRAY. University of Aberdeen.
SKIN FRAGMENTS REMOVED BY NEEDLES
INJECTION
SiR,-We read with interest the recent contributions on this subject, and it occurs to us that some of your readers may not know theAnalgic ’ needle. The action of this needle is first to make an incision the exact diameter of the bore and then, since the bevel is concave and not convex, to dilate this incision and not to punch out any fragment of skin. F. B. DAY John Bell & Croyden, London, W.1.
Director.
PLASMA-CALCIUM IN PRIMARY HYPERPARATHYROIDISM
SiR,-We have, in the past months, been following with great interest the work of Dr. Rose and his collaborators on the diffusible component of the serum-calcium. In his article of Dec. 13 with Dr. Lloyd he refers to discrepancies between his deductions on the binding of calcium to protein and our observations.1 May we comment ? First, Rose and his collaborators arrive at their estimates of calcium bound to the serum-proteins by difference. Ours were direct measurements of the maximal binding of reasonably defined proteins under defined conditions. There is no a-priori reason why, in the conditions of Rose’s estimations, maximal binding should have occurred. Secondly, Rose makes the point that our experiments were not carried out within a physiological pH range. It would, in fact, have been impossible to have achieved the simplicity necessary if we had had to introduce the phosphate ion, the complexity of whose interaction with calcium is well recognised.23 Though as a result of further work in this laboratory4 we would not now do so, in so far as we projected the consequence of our work into the physiological range of pH, we relied on the observations of Ludewig et awl.5 which seemed to indicate that difference in binding would be slight. The conditions we maintdined for both the normal and abnormal albumins were close so that we believe the values for binding represent real differences. The normal circulating albumins contain a fraction of " high binding " material.6 did not at that time discuss the nature or the bond (see Lloyd and Rose). But from work that has continued in this laboratory 1-9 on the general charac-
Thirdly, strength of
we
1. Martin, N. H., Perkins, D. J. Biochem. J. 1953, 54, 642. 2. Marrack, J., Thacker, G. ibid. 1926, 20, 580. 3. Greenwald, I. J. biol. Chem. 1931, 93, 551. 4. Irons, L., Perkins, D. J. Unpublished data. 5. Ludewig, S., Chuantin, S., Masket, A. V. J. biol. Chem. 1942, 143, 753. 6. Martin, N. H., Perkins, D. J. Biochem. J. 1950, 47, 323. 7. Perkins, D. J. ibid. 1952, 51, 487. 8. Perkins, D. J. ibid. 1954, 57, 702. 9. Martin, N. H., Perkins, D. J. Proc. Faraday Soc. 1954, 18, 361.
of kation binding to aminoacids, peptides, and proteins it would appear that as the peptide chain lengthens the average I bond strength weakens, though it cannot be assumed that all ’i binding sites are of the same character. Indeed, we have evidence to the contrary. Fourthly, it is interesting to us that Lloyd and Rose noticed an apparent increase in protein binding of calcium in certain instances in line with our direct observations on patients N and 0. We carried out some ultrafiltration studies at the time that we were studying the calcium binding of the fractionated proteins. Our normal values agreed closely with those of Rose." The only satisfactory general study we carried out on a patient with a parathyroid tumour did not agree. However, her serum-calcium was of the order of 17-5-18 mg. per 100 ml. whereas none of the patients cited by Lloyd and Rose had calcium levels above 13-6 (table u, Lloyd and Rose). ter
This is not the place for a long discussion of minutiae of technique, but we would suggest that in view of the known complexity of the serum-proteins and their known variations in binding capacity, it was time that the simplified equation, enunciated by McLean and Hastings11 twenty years ago was decently buried, and that we attempted, however difficult it may be, to get a more precise view of the interaction of" human proteins with consolidated Donnan calcium. We cannot accept a factor " in a system as complex as serum. In our own work, on a very much simpler system, we computed the Donnan factor from direct measurement of chloride, in each instance checked by sodium. Even then we considered the data in the light of the observation of Scatchard et al. 12 All this is not meant in any way to diminish the practical value of the contribution by Rose, Fanconi,13 and Lloyd. Discrepancies between observations carefully carried out with adequate control are the very seed of advances in knowledge. Chemical Pathology Department, N. H. MARTIN St. George’s Hospital Medical School, D. J. PERKINS. S.W.1. London, DEFIBRINATION SYNDROME IN PREGNANCY
SIR The valuable contribution by Dr. Sharp and his colleagues (Dec. 20) begins with the phrase " Among the complications of late stages of pregnancy... ". Since this implies that episodes such as those described do not occur in early pregnancy, I should like to draw attention to a very recent experience in the university obstetric unit at the City General Hospital, Sheffield. A young married woman, aged 24, was admitted at the 19th week of her first pregnancy complaining of lower abdominal pain and severe vaginal bleeding which had begun a few hours earlier. Her condition deteriorated rapidly, presenting all the features of a severe concealed and revealed accidental htmorrhage, despite the unusually early stage of pregnancy. There was no evidence of pre-eclamptic toxaemia, nor of any other recognised predisposing cause. The shed blood did not clot, and laboratory investigation revealed a major coagulation defect evidently due to gross depletion of fibrinogen. Transfusion of whole blood, plasma, triple-strength reconstituted dried plasma, and pure fibrinogen led to her recovery. In due course, after examination under anaesthesia, rupture of the forewaters and the injection of posterior pituitary extract were followed by spontaneous expulsion of a fresh foetus weighing 8 oz. The placenta showed the typical features of a massive
retroplacental haemorrhage. It is evident that a syndrome indistinguishable from that well known in late presnancv, with accidental ante10. 11. 12. 13.
Rose, G. A. Clin. chim. acta. 1957, 2, 227. McLean, F. C., Hastings, A. B. J. biol. Chem. 1935, 108, 235. Scatchard, G., Scheinberg, I. H., Armstrong, S. H. J. Amer. chem. Soc. 1950, 72, 535. Fanconi, A., Rose, G. A. Quart. J. Med. 1958, 27, 463.
SKIN FRAGMENTS REMOVED BY NEEDLES
INJECTION
SiR,-We read with interest the recent contributions on this subject, and it occurs to us that some of your readers may not know theAnalgic ’ needle. The action of this needle is first to make an incision the exact diameter of the bore and then, since the bevel is concave and not convex, to dilate this incision and not to punch out any fragment of skin. F. B. DAY John Bell & Croyden, London, W.1.
Director.
PLASMA-CALCIUM IN PRIMARY HYPERPARATHYROIDISM
SiR,-We have, in the past months, been following with great interest the work of Dr. Rose and his collaborators on the diffusible component of the serum-calcium. In his article of Dec. 13 with Dr. Lloyd he refers to discrepancies between his deductions on the binding of calcium to protein and our observations.1 May we comment ? First, Rose and his collaborators arrive at their estimates of calcium bound to the serum-proteins by difference. Ours were direct measurements of the maximal binding of reasonably defined proteins under defined conditions. There is no a-priori reason why, in the conditions of Rose’s estimations, maximal binding should have occurred. Secondly, Rose makes the point that our experiments were not carried out within a physiological pH range. It would, in fact, have been impossible to have achieved the simplicity necessary if we had had to introduce the phosphate ion, the complexity of whose interaction with calcium is well recognised.23 Though as a result of further work in this laboratory4 we would not now do so, in so far as we projected the consequence of our work into the physiological range of pH, we relied on the observations of Ludewig et awl.5 which seemed to indicate that difference in binding would be slight. The conditions we maintdined for both the normal and abnormal albumins were close so that we believe the values for binding represent real differences. The normal circulating albumins contain a fraction of " high binding " material.6 did not at that time discuss the nature or the bond (see Lloyd and Rose). But from work that has continued in this laboratory 1-9 on the general charac-
Thirdly, strength of
we
1. Martin, N. H., Perkins, D. J. Biochem. J. 1953, 54, 642. 2. Marrack, J., Thacker, G. ibid. 1926, 20, 580. 3. Greenwald, I. J. biol. Chem. 1931, 93, 551. 4. Irons, L., Perkins, D. J. Unpublished data. 5. Ludewig, S., Chuantin, S., Masket, A. V. J. biol. Chem. 1942, 143, 753. 6. Martin, N. H., Perkins, D. J. Biochem. J. 1950, 47, 323. 7. Perkins, D. J. ibid. 1952, 51, 487. 8. Perkins, D. J. ibid. 1954, 57, 702. 9. Martin, N. H., Perkins, D. J. Proc. Faraday Soc. 1954, 18, 361.
of kation binding to aminoacids, peptides, and proteins it would appear that as the peptide chain lengthens the average I bond strength weakens, though it cannot be assumed that all ’i binding sites are of the same character. Indeed, we have evidence to the contrary. Fourthly, it is interesting to us that Lloyd and Rose noticed an apparent increase in protein binding of calcium in certain instances in line with our direct observations on patients N and 0. We carried out some ultrafiltration studies at the time that we were studying the calcium binding of the fractionated proteins. Our normal values agreed closely with those of Rose." The only satisfactory general study we carried out on a patient with a parathyroid tumour did not agree. However, her serum-calcium was of the order of 17-5-18 mg. per 100 ml. whereas none of the patients cited by Lloyd and Rose had calcium levels above 13-6 (table u, Lloyd and Rose). ter
This is not the place for a long discussion of minutiae of technique, but we would suggest that in view of the known complexity of the serum-proteins and their known variations in binding capacity, it was time that the simplified equation, enunciated by McLean and Hastings11 twenty years ago was decently buried, and that we attempted, however difficult it may be, to get a more precise view of the interaction of" human proteins with consolidated Donnan calcium. We cannot accept a factor " in a system as complex as serum. In our own work, on a very much simpler system, we computed the Donnan factor from direct measurement of chloride, in each instance checked by sodium. Even then we considered the data in the light of the observation of Scatchard et al. 12 All this is not meant in any way to diminish the practical value of the contribution by Rose, Fanconi,13 and Lloyd. Discrepancies between observations carefully carried out with adequate control are the very seed of advances in knowledge. Chemical Pathology Department, N. H. MARTIN St. George’s Hospital Medical School, D. J. PERKINS. S.W.1. London, DEFIBRINATION SYNDROME IN PREGNANCY
SIR The valuable contribution by Dr. Sharp and his colleagues (Dec. 20) begins with the phrase " Among the complications of late stages of pregnancy... ". Since this implies that episodes such as those described do not occur in early pregnancy, I should like to draw attention to a very recent experience in the university obstetric unit at the City General Hospital, Sheffield. A young married woman, aged 24, was admitted at the 19th week of her first pregnancy complaining of lower abdominal pain and severe vaginal bleeding which had begun a few hours earlier. Her condition deteriorated rapidly, presenting all the features of a severe concealed and revealed accidental htmorrhage, despite the unusually early stage of pregnancy. There was no evidence of pre-eclamptic toxaemia, nor of any other recognised predisposing cause. The shed blood did not clot, and laboratory investigation revealed a major coagulation defect evidently due to gross depletion of fibrinogen. Transfusion of whole blood, plasma, triple-strength reconstituted dried plasma, and pure fibrinogen led to her recovery. In due course, after examination under anaesthesia, rupture of the forewaters and the injection of posterior pituitary extract were followed by spontaneous expulsion of a fresh foetus weighing 8 oz. The placenta showed the typical features of a massive
retroplacental haemorrhage. It is evident that a syndrome indistinguishable from that well known in late presnancv, with accidental ante10. 11. 12. 13.
Rose, G. A. Clin. chim. acta. 1957, 2, 227. McLean, F. C., Hastings, A. B. J. biol. Chem. 1935, 108, 235. Scatchard, G., Scheinberg, I. H., Armstrong, S. H. J. Amer. chem. Soc. 1950, 72, 535. Fanconi, A., Rose, G. A. Quart. J. Med. 1958, 27, 463.