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SERUM-GONADOTROPHINS AFTER OXYTOCIN IN MAN
735 or to continue the process of the precipitation of the calcium salts in the urine. This is supported by the highly significant difference of the Mg/Ca ratio between controls and patients with renal stones without obvious cause and our other data. Since this ratio can be changed by changes in
necessary to initiate
both elements, this necessitated the study of this ratio under any concentration of these elements. If we had compared groups (of controls and patients) with the same excretion of calcium then the ratio would reflect fluctuations of the magnesium only. 34 of their " normal " group of 83 subjects are hypercalciurics, which is an unexpectedly large proportion (41%) for a normally constituted population. These hypercalciuric subjects are potential stone formers and it is even possible that some may have already formed undiagnosed renal stones. The fact that their Mg/Ca ratio is similar to their and our stone formers’ is not surprising, but rather to be expected. D. G. OREOPOULOS Department of Medicine, M. G. MCGEOWN Queen’s University, M. A. O. SOYANNWO. Belfast BT12 6BJ.
SERUM-GONADOTROPHINS AFTER OXYTOCIN IN MAN
SIR,-There have been very few studies in man on the gonadotrophin-stimulating effect of oxytocin, perhaps because only non-specific bioassay methods have hitherto been available for such studies. We have therefore estimated serum-level in seven men, aged 19-21, after the rapid intravenous (over 3 minutes) injection of 2 i.u. of synthetic oxytocin (’ SyntocinonSandoz). Blood-samples were collected at times 0, 10, 20,30,45) 60, 90, and 120 minutes, and radioimmunoassay was carried out according to the method of one of us (P. F.). 12 We found a highly significant rise of follicle-stimulating hormone (F.s.H.) and a slight fall in luteinising hormone (L.H.). MEAN SERUM-GONADOTROPHIN LEVELS
(IN MILLI-I.U.
HÆMOLYTIC-URÆMIC SYNDROME SiR,—As mentioned in your annotation (Aug. 3, p. 271), thrombi in the glomerular tufts are common, and fibrinoid necrosis and intraluminal thrombi in the afferent arterioles are possible, in patients with the hsemolytic-uraemic syndrome. In some patients with this syndrome accelerated intravascular coagulation can be proved 1-3 or shown to be probable.4 To demonstrate low-grade intravascular coagulation, tests more sensitive than the standard ones are needed (1-nbrinogen
catabolism, fibrin-split products).2 Heparin treatment, as proposed by several workers whom you cite, can only prevent increasing thrombosis and further renal damage. Condie et al.5 proved that the changes in the kidney provoked by the Schwartzman reaction (resembling the lesions seen in the hsemolytic-urasmic syndrome) were reversible by streptokinase. Because of our unfavourable experience with heparin therapy alone (two of three children treated with heparin and peritoneal dialysis died), we therefore tried to lyse the thrombi with streptokinase and continued the treatment with heparin. The
course
of
treatment
in
a
nine-month-old infant with the
haemolytic-ursemic syndrome is shown in the accompanying figure. This child was referred to our department on Nov. 16, 1967. On Nov. 9 the child had had bloody diarrhoea, and she had been admitted to another hospital on Nov. 13. A normal blood-urea (20 mg. per 100 ml.) and haemoglobin (13-7 g. per 100 ml.) were found. On Nov. 15 the hxmoglobin was 5-6 g. per 100 ml. Packed cells noted on Nov. 16, 1967. 1. 2.
were
transfused. Haematuria
was
Desmit, E., Hart, H. C., Helleman, P. W., Tiddens, H. A. W. M. Proc. Europ. Dialysis Transpl. Ass. 1966, 2, 68. Brian, M. C., Baker, L. R. I., McBride, J. A., Rubenberg, M. Q. Jl
Med. 1967, 36, 608. Monnens, L., Schretlen, E. Acta pœdiat., Stockh. 1967, 56, 436. Piel, F. C., Hadley, K., Phibbs, R. H. Pediat. Res. 1967, 1, 211. 5. Condie, R. M., Hong, C. Y., Good, R. A. J. Lab. clin. Med. 1957, 50, 803. 3. 4.
OF INTERNATIONAL
2 OF HUMAN MENOPAUSAL GONADOTROPHIN PER ml. OF SERUM) IN 7 MEN, AGED 19-21, BEFORE AND AFTER RAPID INTRAVENOUS INJECTION (OVER 3 MINUTES) OF 2 LU. OF REFERENCE PREPARATION NO.
OXYTOCIN
known whether
our results have any physiological the very low dose which we used (2 I.U. of oxytocin in total blood-volume roughly corresponds to 1 milliunit per ml. plasma) could argue in favour of that. Furthermore, injection of 2 l.u. of synthetic lypressin (Sandoz) is followed by no change of F.S.H. and L.H. blood-levels, while injection of 2 l.u. of total natural extract (’ Post-Hypophyse ’, Choay) produces an increase of both gonadotrophins.3 But one must remember that, while synthetic oxytocin is not contaminated by other peptides like vasopressin or other releasing factors as are natural extracts, there are other types of impurities (dimers of oxytocin, for example) which could have a releasing effect on F.s.H. greater than their oxytocic effect, though this has yet to be investigated.
It is
not
implication, though
J. J. L. is in training as a research-worker for the Fonds National de la Recherche Scientifique. Institut de Médecine, Département de Clinique et de Pathologie Médicales, Université de Liège, Belgium. 1.
2. 3.
J. J. LEGROS P. FRANCHIMONT.
Franchimont, P. in Le dosage des hormones hypophysaires somatotrope et gonadotropes et son application en clinique (edited by S. A. Arscia). Brussels, 1966. Pranchimont, P. in Protein and Polypeptides Hormones (edited by M. Margoulies); vol. I, p. 99. Amsterdam, 1968. Franchimont, P., Legros, J. J. Annls Endocr. (in the press).
Effect of streptokinase-heparin treatment with haemolytic-uraemic syndrome.
on
nine-month-old infant
necessary to initiate
both elements, this necessitated the study of this ratio under any concentration of these elements. If we had compared groups (of controls and patients) with the same excretion of calcium then the ratio would reflect fluctuations of the magnesium only. 34 of their " normal " group of 83 subjects are hypercalciurics, which is an unexpectedly large proportion (41%) for a normally constituted population. These hypercalciuric subjects are potential stone formers and it is even possible that some may have already formed undiagnosed renal stones. The fact that their Mg/Ca ratio is similar to their and our stone formers’ is not surprising, but rather to be expected. D. G. OREOPOULOS Department of Medicine, M. G. MCGEOWN Queen’s University, M. A. O. SOYANNWO. Belfast BT12 6BJ.
SERUM-GONADOTROPHINS AFTER OXYTOCIN IN MAN
SIR,-There have been very few studies in man on the gonadotrophin-stimulating effect of oxytocin, perhaps because only non-specific bioassay methods have hitherto been available for such studies. We have therefore estimated serum-level in seven men, aged 19-21, after the rapid intravenous (over 3 minutes) injection of 2 i.u. of synthetic oxytocin (’ SyntocinonSandoz). Blood-samples were collected at times 0, 10, 20,30,45) 60, 90, and 120 minutes, and radioimmunoassay was carried out according to the method of one of us (P. F.). 12 We found a highly significant rise of follicle-stimulating hormone (F.s.H.) and a slight fall in luteinising hormone (L.H.). MEAN SERUM-GONADOTROPHIN LEVELS
(IN MILLI-I.U.
HÆMOLYTIC-URÆMIC SYNDROME SiR,—As mentioned in your annotation (Aug. 3, p. 271), thrombi in the glomerular tufts are common, and fibrinoid necrosis and intraluminal thrombi in the afferent arterioles are possible, in patients with the hsemolytic-uraemic syndrome. In some patients with this syndrome accelerated intravascular coagulation can be proved 1-3 or shown to be probable.4 To demonstrate low-grade intravascular coagulation, tests more sensitive than the standard ones are needed (1-nbrinogen
catabolism, fibrin-split products).2 Heparin treatment, as proposed by several workers whom you cite, can only prevent increasing thrombosis and further renal damage. Condie et al.5 proved that the changes in the kidney provoked by the Schwartzman reaction (resembling the lesions seen in the hsemolytic-urasmic syndrome) were reversible by streptokinase. Because of our unfavourable experience with heparin therapy alone (two of three children treated with heparin and peritoneal dialysis died), we therefore tried to lyse the thrombi with streptokinase and continued the treatment with heparin. The
course
of
treatment
in
a
nine-month-old infant with the
haemolytic-ursemic syndrome is shown in the accompanying figure. This child was referred to our department on Nov. 16, 1967. On Nov. 9 the child had had bloody diarrhoea, and she had been admitted to another hospital on Nov. 13. A normal blood-urea (20 mg. per 100 ml.) and haemoglobin (13-7 g. per 100 ml.) were found. On Nov. 15 the hxmoglobin was 5-6 g. per 100 ml. Packed cells noted on Nov. 16, 1967. 1. 2.
were
transfused. Haematuria
was
Desmit, E., Hart, H. C., Helleman, P. W., Tiddens, H. A. W. M. Proc. Europ. Dialysis Transpl. Ass. 1966, 2, 68. Brian, M. C., Baker, L. R. I., McBride, J. A., Rubenberg, M. Q. Jl
Med. 1967, 36, 608. Monnens, L., Schretlen, E. Acta pœdiat., Stockh. 1967, 56, 436. Piel, F. C., Hadley, K., Phibbs, R. H. Pediat. Res. 1967, 1, 211. 5. Condie, R. M., Hong, C. Y., Good, R. A. J. Lab. clin. Med. 1957, 50, 803. 3. 4.
OF INTERNATIONAL
2 OF HUMAN MENOPAUSAL GONADOTROPHIN PER ml. OF SERUM) IN 7 MEN, AGED 19-21, BEFORE AND AFTER RAPID INTRAVENOUS INJECTION (OVER 3 MINUTES) OF 2 LU. OF REFERENCE PREPARATION NO.
OXYTOCIN
known whether
our results have any physiological the very low dose which we used (2 I.U. of oxytocin in total blood-volume roughly corresponds to 1 milliunit per ml. plasma) could argue in favour of that. Furthermore, injection of 2 l.u. of synthetic lypressin (Sandoz) is followed by no change of F.S.H. and L.H. blood-levels, while injection of 2 l.u. of total natural extract (’ Post-Hypophyse ’, Choay) produces an increase of both gonadotrophins.3 But one must remember that, while synthetic oxytocin is not contaminated by other peptides like vasopressin or other releasing factors as are natural extracts, there are other types of impurities (dimers of oxytocin, for example) which could have a releasing effect on F.s.H. greater than their oxytocic effect, though this has yet to be investigated.
It is
not
implication, though
J. J. L. is in training as a research-worker for the Fonds National de la Recherche Scientifique. Institut de Médecine, Département de Clinique et de Pathologie Médicales, Université de Liège, Belgium. 1.
2. 3.
J. J. LEGROS P. FRANCHIMONT.
Franchimont, P. in Le dosage des hormones hypophysaires somatotrope et gonadotropes et son application en clinique (edited by S. A. Arscia). Brussels, 1966. Pranchimont, P. in Protein and Polypeptides Hormones (edited by M. Margoulies); vol. I, p. 99. Amsterdam, 1968. Franchimont, P., Legros, J. J. Annls Endocr. (in the press).
Effect of streptokinase-heparin treatment with haemolytic-uraemic syndrome.
on
nine-month-old infant