1075 months. 22 of the 23 patients with null-cell A.L.L. still in their first remission when last seen. 1 had a hsematological relapse twenty-four months after diagnosis; this patient had the highest initial white-cell count of the null group. In the T-cell group 4 patients have died. 1 died with Escherichia coli septicaemia and meningitis during the first week of treatment. 2 had haematological relapses after six and eight months of remission, followed by central-nervous-system relapse and death sixteen and ten months, respectively, after diagnosis. A fourth died at four months with a clinical septicaemia. Necropsy revealed infiltration of lungs and intestinal tract by cells with the histological appearances of a highly malignant lymphoma. The original bone-marrow appearance had been indistinguishable from A.L.L. 1 patient with T-cell leukeemia remains in remission, seventeen months after diagnosis. The numbers are small; nevertheless the difference in prognosis between T-cell leukaemia and null-cell A.L.L. is striking. The difference cannot simply be explained by a high initial white-cell count. The 1 child with T-cell leukaemia who is still in remission had an initial white-cell count of 107 x 101/1, and 2 others who died had counts of less than 20 x 109/1. The presence of a T-cell marker on blasts may prove to be a better single indicator of prognosis than any of the "bad risk" factors now used. If further large series confirm the poor prognosis of T-cell leukaemia different chemotherapy regimens for this group may be needed. Departments of Hæmatology M. M. REID and Child Health, A. W. CRAFT Royal Victoria Infirmary, Newcastle upon Tyne NE 1 4LP W. WALKER
the concomitant formation of antiand adenosine) will limit the growth of platelet clumps in vivo. Because we had used arachidonate rather than adenosine diphosphate (A.D.P.) to induce aggregation we have repeated our experiments, using A.D.P. as the aggregating agent, with 15-H.P.A.A. or 13-hydroperoxylinoleic acid (13-H.P.L.A.)2 to inhibit prostacyclin formation. First we took fresh rings of rabbit aorta or suspensions of intimal cells scraped from a rabbit aorta and found that A.D.P. incubated with them gradually disappeared (fig. 1). These experiments confirmed that our preparations, like those of Heyns et a1.9 and Lieberman et al.,1O had A.D.p.-ase activity. Incubation with concentrations of 15-H.P.A.A. (20-50 g/ml) or 13-H.P.L.A. (20-50 p.g/ml) which abolish prostacyclin formation,3 did not affect the rate of disappearance of added A.D.P. The inhibitors of prostacyclin formation are thus specific and do not affect A.D.p.-ase. Finally, we assessed the antiaggregatory properties of the intimal cells under conditions when they could (no treatment) or could not (15 min prior incubation with 13-H.P.L.A. at 20-50 p.g/ml) form prostacyclin. The intimal cells lost their ability to inhibit A.D.P.-induced aggregation when prostacyclin formation was prevented (fig. 2). Similar results were obtained with intimal cells and aortic or mesenteric rings.
twenty-four
struction of
A.D.P.
were
aggregatory
A.M.P.
(with
12. Salmon, J. A., Smith, D. R., Flower, R. chim. biophys. Acta. (in the press).
J., Moncada, S., Vane, J. R. Bio-
ANTITHROMBOTIC PROPERTIES OF VASCULAR ENDOTHELIUM
SIR,-We have found that vascular tissue generates prosta-
cyclin (P.G.X, P.G.I2), a prostaglandin which inhibits human platelet aggregation’-4 very much more powerfully than does P.G.D2, p.G.E1’3 or adenosine.s It acts through stimulation of platelet adenyl cyclase.6.7 The enzyme which generates prostacyclin is concentrated in the intimal cells,8 and we have proposed that formation of prostacyclin (from endoperoxides in the vascular wall or released by platelets attempting to clump) is the main mechanism by which healthy vascular endothelium prevents deposition of platelet clumps.4 In 1974, Heyns et a1.9 demonstrated an A.D.P.-ase in an intimal extract from human aorta. They proposed that this enzyme was responsible for the antiaggregating effect observed when intimal extracts were incubated with human platelet-rich plasma before induction of aggregation. However, prostacyclin formation seems a more likely explanation of this antiaggregatory activity, for in similar experiments4.8 we demonstrated prostacyclin generation, and antiaggregatory activity was abolished when the tissue was incubated with a specific inhibitor of prostacyclin synthetase, 15-hydroperoxyarachidonic acid (15-H.P.A.A.). Lewis and his colleagues have now revived the A.D.P:-ase hypothesis. They found A.D.p.-ase activity in microsomes from rabbit aorta’O and in arterial ringsll and suggested that de1.Moncada,
r
I-Breakdown of A.D.P.
,
endothelial cell
suspensions. by (1-4 tmol/1) induced dose-dependent aggregation in 0.5 ml samples of human platelet-rich plasma. A.D.P. was then stirred at 37 °C in platelet-poor plasma with endothelial cells (36 000) in a total volume of 200 1 and samples giving 4 p.mol/1 A.D.P. in 500 nl plateletrich plasma were tested for their ability to induce aggregation. The Fig.
A.D.P.
endothelial cells were incubated on ice for 15 min with 15-H.P.A.A. (50 pLg/ml) before addition to the platelet-poor plasma. Although incubation for 2 min hardly changed the A.D.P. activity, incubation for 7 min reduced it to less than 50%.
S., Gryglewski, R., Bunting, S., Vane, J. R. Nature, 1976, 263,
663. 2
Moncada, S., Gryglewski, R. J., Bunting, S., Vane, J. R. Prostaglandins,
1976, 12, 715. 3. Gryglewski, R. J.,
Bunting, S., Moncada, S., Flower,
R. J., Vane, J. R. ibid.
p. 685. 4. Bunting, S., Gryglewski, R., Moncada, S., Vane, J. R. ibid. p. 897. 5. Born,G . V.R. Nature, 1962, 194, 927. 6.Tateson, J.E., Moncada, S., Vane, J. R. Prostaglandins, 1977, 13, 389. 7. Gorman, R. R., Bunting, S., Miller, O.V.ibid.p. 377. 8 Herman, A. G., Moncada, S., Vane, J. R.Archs Int. Pharm, Therap. 1977,
227, 162.
9. Heyns,
A. du P., Van Den Berg, G. H., Thromb.Diath.hœmorrh. 1974, 32, 417.
Potgieter,
G. M.,
Retief, F. P.
10.Lieberman, G. E., Lewis, G.P., Peters, T. J.Lancet, 1977, ii, 330. 11.Lewis, G. P., Lieberman, G. E., Westwick, J. Br. J. Pharmac.(in the
press).
16
Fig. 2-Inhibition of aggregation by endothelial cells. Endothelial cells (36 000) from an indomethacin-treated rabbit (10 mg/kg) when incubated in platelet-rich plasma 2 min before the addition of A.D.P. prevented A.D.P.-induced aggregation. Pretreatment of the cells with a prostacyclin synthetase inhibitor (15-H.P.A.A., 50 jjtg/ml) completely abolished the inhibitory activity of the cell suspension.
1076 The inhibition of platelet to an
aggregation by prostacyclin is due
increase in platelet cyclic adenosine monophosphate
(cA.M.P.).6,7 The incubation of aortic pieces in platelet-rich plasma leads to an inhibition of platelet aggregation which is paralleled by an increase in platelet CA.M.P., both effects being prevented by prostacyclin-synthetase inhibitors.’3 15-H.P.A.A. 13-H.P.L.A. do not inhibit the A.D.P.-ase in the rabbit aorta and it is, therefore, unlikely that platelet CA.M.P. levels are modulated via an A.D.P.-ase. Prostacyclin is synthesised by vascular tissues,2,4 including those of man,14 by means of an enzyme in intimal cells,8 and can prevent or even reverse platelet aggregation.2 These and our latest findings strongly suggest that prostacyclin formation is the main defence of the intima against the deposition of platelet clumps. This may be reinforced by an A.D.P.-ase system but it would require the involvement of A.D.P. released from platelets 15 or red cells" in intravascular thrombus formation, and there is now evidence that A.D.P. release by platelets is not necessary for their aggregation. 17 or
We thank Miss P. Reed for technical assistance.
Wellcome Research Laboratories, Beckenham BR3 3BS
S. BUNTING S. MONCADA
J. R. VANE
JOINING UP THE LOWER GUT SIR,-Your editorial (Nov. 5, p. 963) provides a concise, but slightly misleading, summary of recent studies of the technique of colorectal anastomosis. I think you are correct to conclude that the case for single-layer anastomosis of the intestine remains sub judice. If single-layer techniques do have advantages in rectal anastomosis then the rectum would seem to be a special case, for there is no convincing evidence that such techniques have any particular merit elsewhere in the intestine. In eight separate experimental studies of intestinal anastomosis, measurements of intestinal healing showed that the single-layer technique of anastomosis was superior to the stanmethod in three studies and not significantly dard different in five.’ Furthermore, in nine separate clinical studies of single-layer anastomosis in the large intestine in more than 600 patients the clinical frequency of anastomotic dehiscence ranged from zero to 14% As you point out, the evidence for or against the single-layer anastomosis in the rectum is conflicting, but it is unlikely that success or failure with the single-layer method can be explained by differences in suture technique or suture materials. Two controlled trials2·3 of low colorectal anastomosis have yielded very different results but, contrary to what you say, the suture technique was similar in these studies. Information regarding the relative merits of different suture materials in the rectum is lacking but surgeons have achieved highly acceptable results in oesophageal anastomosis with various nonabsorbable suture materials, including silk, linen, wire, and
two-layer
rectal anastomosis may be easy, difficult, or very difficult depending on the pelvic anatomy and the extent of the rectal excision. The surgeon who accepts the difficult cases and treats a high proportion of his cases by anterior resection can reasonably expect a higher incidence of anastomotic dehiscence than the surgeon who avoids very difficult operations and more frequently reports to an abdominoperineal excision of the rectum. University Surgical Unit, Royal Infirmary,
THOMAS T. IRVIN
Sheffield S6 3DA
HYPERGLYCÆMIC EFFECT OF SYNTHETIC SALMON CALCITONIN
SIR,-Little is known of the effects of calcitonin on glucose metabolism. We have seen a striking increase in blood-glucose after a single subcutaneous injection of synthetic salmon calcitonin (s.c.T.) to patients with untreated Paget’s disease of bone.
After a 12 hour fast nine patients were injected with 100 M.R.C. units of synthetic s.c.T. (’Calcimar’, Armour Pharmaceutical Co). Three patients were also injected with the vehicle alone. Serum glucose, calcium, and phosphate and plasmainsulin were measured at 0, 3, 6, 8, 10, and 12 h. As shown in the figure a single dose of s.c.T. provoked a progressive increase in glucose with a mean peak of 119 mg/dl at 6-h (normal range 80-100 mg/dl). Basal plasma immunoreactive-insulin levels fell from 3-6 to 2.5 U/ml (detection limit of the assay) in both experimental and control studies. A strong negative correlation was found between serum calcium and glucose
(r=0.84, p=0.03). Acute administration of
synthetic human calcitonin’ or of volunteers healthy significantly impaired glucose tolerance. Our results confirm that calcitonin alters glucose metabolism, reflected in our study by a progressive increase in basal glucose. Since serum-calcium has an important effect on insulin secretion3 it is tempting to speculate on a possible suppressive effect of s.c.T. on insulin secretion through reduction of serum-calcium. Whatever the mechanism the possibility of a transient, or even a permanent, diabetic state secondary to chronic s.c.T. administration to patients with Paget’s disease of bone deserves serious consideration. s.c.T.2
to
This work was supported in part by grants from the C. 0. Monat, H. K. Detweiler, and McDonald-Stewart Foundations. We thank Dr
1.
Ziegler, R., Bellwinkel, S., Schmitchen, D., Minne, H. Hormone Metab. Res.
1972, 4, 60. Blahos, J. Zvoboda, J., Hoschl, C. Endokrinologie, 1976, 68, 226. 3. Yasuda, K., Hurukawa, Y., Okuyama, M., Kikuehi, M., Yoshinaga, K. New Engl. J. Med. 1975, 292, 501.
2.
polypropylene. Suture techniques
can be compared only within the context controlled clinical trial and it is unwise to conclude anything from differences between trials unless all the variables which may affect the results are known to be similarly disposed in these studies. This is particularly true of colorectal anastomosis. Success or failure may depend on the skill and experience of the surgeon and on the difficulty of the operation. Colo-
of
a
13. Best, L.
C., Martin, T. J., Russell, R. G. G., Preston, F. E. Nature, 1977, 267, 851. 14. Moncada, S., Higgs, E. A., Vane, J. R. Lancet, 1977, i, 17. 15. Spaet, T. H., Zucker, M. B. Am. J. Physiol. 1964, 206, 1267. 16. Gaarder, A., Jonson, J., Laland, S., Hellem, A., Owren, P. A. Nature, 1961, 192, 531. 17. Charo, I. F., Feinman, R. D, Detwiler, T. C., Smith, J. B., Ingerman, C. H., Silver, M. J. ibid. 1977, 269, 68. 1. Irvin, T. T. CH.M. thesis, University of Aberdeen, 1974. 2. Everett, W. G. Br. J. Surg. 1975, 62, 135. 3. Goligher, J. C., Lee, P. W. G., Simkins, K. C., Lintott, D. J. ibid. 1977, 64, 609.
Serum glucose and calcium levels after S.C.T.
acute
administration of
the concomitant formation of antiand adenosine) will limit the growth of platelet clumps in vivo. Because we had used arachidonate rather than adenosine diphosphate (A.D.P.) to induce aggregation we have repeated our experiments, using A.D.P. as the aggregating agent, with 15-H.P.A.A. or 13-hydroperoxylinoleic acid (13-H.P.L.A.)2 to inhibit prostacyclin formation. First we took fresh rings of rabbit aorta or suspensions of intimal cells scraped from a rabbit aorta and found that A.D.P. incubated with them gradually disappeared (fig. 1). These experiments confirmed that our preparations, like those of Heyns et a1.9 and Lieberman et al.,1O had A.D.p.-ase activity. Incubation with concentrations of 15-H.P.A.A. (20-50 g/ml) or 13-H.P.L.A. (20-50 p.g/ml) which abolish prostacyclin formation,3 did not affect the rate of disappearance of added A.D.P. The inhibitors of prostacyclin formation are thus specific and do not affect A.D.p.-ase. Finally, we assessed the antiaggregatory properties of the intimal cells under conditions when they could (no treatment) or could not (15 min prior incubation with 13-H.P.L.A. at 20-50 p.g/ml) form prostacyclin. The intimal cells lost their ability to inhibit A.D.P.-induced aggregation when prostacyclin formation was prevented (fig. 2). Similar results were obtained with intimal cells and aortic or mesenteric rings.
twenty-four
struction of
A.D.P.
were
aggregatory
A.M.P.
(with
12. Salmon, J. A., Smith, D. R., Flower, R. chim. biophys. Acta. (in the press).
J., Moncada, S., Vane, J. R. Bio-
ANTITHROMBOTIC PROPERTIES OF VASCULAR ENDOTHELIUM
SIR,-We have found that vascular tissue generates prosta-
cyclin (P.G.X, P.G.I2), a prostaglandin which inhibits human platelet aggregation’-4 very much more powerfully than does P.G.D2, p.G.E1’3 or adenosine.s It acts through stimulation of platelet adenyl cyclase.6.7 The enzyme which generates prostacyclin is concentrated in the intimal cells,8 and we have proposed that formation of prostacyclin (from endoperoxides in the vascular wall or released by platelets attempting to clump) is the main mechanism by which healthy vascular endothelium prevents deposition of platelet clumps.4 In 1974, Heyns et a1.9 demonstrated an A.D.P.-ase in an intimal extract from human aorta. They proposed that this enzyme was responsible for the antiaggregating effect observed when intimal extracts were incubated with human platelet-rich plasma before induction of aggregation. However, prostacyclin formation seems a more likely explanation of this antiaggregatory activity, for in similar experiments4.8 we demonstrated prostacyclin generation, and antiaggregatory activity was abolished when the tissue was incubated with a specific inhibitor of prostacyclin synthetase, 15-hydroperoxyarachidonic acid (15-H.P.A.A.). Lewis and his colleagues have now revived the A.D.P:-ase hypothesis. They found A.D.p.-ase activity in microsomes from rabbit aorta’O and in arterial ringsll and suggested that de1.Moncada,
r
I-Breakdown of A.D.P.
,
endothelial cell
suspensions. by (1-4 tmol/1) induced dose-dependent aggregation in 0.5 ml samples of human platelet-rich plasma. A.D.P. was then stirred at 37 °C in platelet-poor plasma with endothelial cells (36 000) in a total volume of 200 1 and samples giving 4 p.mol/1 A.D.P. in 500 nl plateletrich plasma were tested for their ability to induce aggregation. The Fig.
A.D.P.
endothelial cells were incubated on ice for 15 min with 15-H.P.A.A. (50 pLg/ml) before addition to the platelet-poor plasma. Although incubation for 2 min hardly changed the A.D.P. activity, incubation for 7 min reduced it to less than 50%.
S., Gryglewski, R., Bunting, S., Vane, J. R. Nature, 1976, 263,
663. 2
Moncada, S., Gryglewski, R. J., Bunting, S., Vane, J. R. Prostaglandins,
1976, 12, 715. 3. Gryglewski, R. J.,
Bunting, S., Moncada, S., Flower,
R. J., Vane, J. R. ibid.
p. 685. 4. Bunting, S., Gryglewski, R., Moncada, S., Vane, J. R. ibid. p. 897. 5. Born,G . V.R. Nature, 1962, 194, 927. 6.Tateson, J.E., Moncada, S., Vane, J. R. Prostaglandins, 1977, 13, 389. 7. Gorman, R. R., Bunting, S., Miller, O.V.ibid.p. 377. 8 Herman, A. G., Moncada, S., Vane, J. R.Archs Int. Pharm, Therap. 1977,
227, 162.
9. Heyns,
A. du P., Van Den Berg, G. H., Thromb.Diath.hœmorrh. 1974, 32, 417.
Potgieter,
G. M.,
Retief, F. P.
10.Lieberman, G. E., Lewis, G.P., Peters, T. J.Lancet, 1977, ii, 330. 11.Lewis, G. P., Lieberman, G. E., Westwick, J. Br. J. Pharmac.(in the
press).
16
Fig. 2-Inhibition of aggregation by endothelial cells. Endothelial cells (36 000) from an indomethacin-treated rabbit (10 mg/kg) when incubated in platelet-rich plasma 2 min before the addition of A.D.P. prevented A.D.P.-induced aggregation. Pretreatment of the cells with a prostacyclin synthetase inhibitor (15-H.P.A.A., 50 jjtg/ml) completely abolished the inhibitory activity of the cell suspension.
1076 The inhibition of platelet to an
aggregation by prostacyclin is due
increase in platelet cyclic adenosine monophosphate
(cA.M.P.).6,7 The incubation of aortic pieces in platelet-rich plasma leads to an inhibition of platelet aggregation which is paralleled by an increase in platelet CA.M.P., both effects being prevented by prostacyclin-synthetase inhibitors.’3 15-H.P.A.A. 13-H.P.L.A. do not inhibit the A.D.P.-ase in the rabbit aorta and it is, therefore, unlikely that platelet CA.M.P. levels are modulated via an A.D.P.-ase. Prostacyclin is synthesised by vascular tissues,2,4 including those of man,14 by means of an enzyme in intimal cells,8 and can prevent or even reverse platelet aggregation.2 These and our latest findings strongly suggest that prostacyclin formation is the main defence of the intima against the deposition of platelet clumps. This may be reinforced by an A.D.P.-ase system but it would require the involvement of A.D.P. released from platelets 15 or red cells" in intravascular thrombus formation, and there is now evidence that A.D.P. release by platelets is not necessary for their aggregation. 17 or
We thank Miss P. Reed for technical assistance.
Wellcome Research Laboratories, Beckenham BR3 3BS
S. BUNTING S. MONCADA
J. R. VANE
JOINING UP THE LOWER GUT SIR,-Your editorial (Nov. 5, p. 963) provides a concise, but slightly misleading, summary of recent studies of the technique of colorectal anastomosis. I think you are correct to conclude that the case for single-layer anastomosis of the intestine remains sub judice. If single-layer techniques do have advantages in rectal anastomosis then the rectum would seem to be a special case, for there is no convincing evidence that such techniques have any particular merit elsewhere in the intestine. In eight separate experimental studies of intestinal anastomosis, measurements of intestinal healing showed that the single-layer technique of anastomosis was superior to the stanmethod in three studies and not significantly dard different in five.’ Furthermore, in nine separate clinical studies of single-layer anastomosis in the large intestine in more than 600 patients the clinical frequency of anastomotic dehiscence ranged from zero to 14% As you point out, the evidence for or against the single-layer anastomosis in the rectum is conflicting, but it is unlikely that success or failure with the single-layer method can be explained by differences in suture technique or suture materials. Two controlled trials2·3 of low colorectal anastomosis have yielded very different results but, contrary to what you say, the suture technique was similar in these studies. Information regarding the relative merits of different suture materials in the rectum is lacking but surgeons have achieved highly acceptable results in oesophageal anastomosis with various nonabsorbable suture materials, including silk, linen, wire, and
two-layer
rectal anastomosis may be easy, difficult, or very difficult depending on the pelvic anatomy and the extent of the rectal excision. The surgeon who accepts the difficult cases and treats a high proportion of his cases by anterior resection can reasonably expect a higher incidence of anastomotic dehiscence than the surgeon who avoids very difficult operations and more frequently reports to an abdominoperineal excision of the rectum. University Surgical Unit, Royal Infirmary,
THOMAS T. IRVIN
Sheffield S6 3DA
HYPERGLYCÆMIC EFFECT OF SYNTHETIC SALMON CALCITONIN
SIR,-Little is known of the effects of calcitonin on glucose metabolism. We have seen a striking increase in blood-glucose after a single subcutaneous injection of synthetic salmon calcitonin (s.c.T.) to patients with untreated Paget’s disease of bone.
After a 12 hour fast nine patients were injected with 100 M.R.C. units of synthetic s.c.T. (’Calcimar’, Armour Pharmaceutical Co). Three patients were also injected with the vehicle alone. Serum glucose, calcium, and phosphate and plasmainsulin were measured at 0, 3, 6, 8, 10, and 12 h. As shown in the figure a single dose of s.c.T. provoked a progressive increase in glucose with a mean peak of 119 mg/dl at 6-h (normal range 80-100 mg/dl). Basal plasma immunoreactive-insulin levels fell from 3-6 to 2.5 U/ml (detection limit of the assay) in both experimental and control studies. A strong negative correlation was found between serum calcium and glucose
(r=0.84, p=0.03). Acute administration of
synthetic human calcitonin’ or of volunteers healthy significantly impaired glucose tolerance. Our results confirm that calcitonin alters glucose metabolism, reflected in our study by a progressive increase in basal glucose. Since serum-calcium has an important effect on insulin secretion3 it is tempting to speculate on a possible suppressive effect of s.c.T. on insulin secretion through reduction of serum-calcium. Whatever the mechanism the possibility of a transient, or even a permanent, diabetic state secondary to chronic s.c.T. administration to patients with Paget’s disease of bone deserves serious consideration. s.c.T.2
to
This work was supported in part by grants from the C. 0. Monat, H. K. Detweiler, and McDonald-Stewart Foundations. We thank Dr
1.
Ziegler, R., Bellwinkel, S., Schmitchen, D., Minne, H. Hormone Metab. Res.
1972, 4, 60. Blahos, J. Zvoboda, J., Hoschl, C. Endokrinologie, 1976, 68, 226. 3. Yasuda, K., Hurukawa, Y., Okuyama, M., Kikuehi, M., Yoshinaga, K. New Engl. J. Med. 1975, 292, 501.
2.
polypropylene. Suture techniques
can be compared only within the context controlled clinical trial and it is unwise to conclude anything from differences between trials unless all the variables which may affect the results are known to be similarly disposed in these studies. This is particularly true of colorectal anastomosis. Success or failure may depend on the skill and experience of the surgeon and on the difficulty of the operation. Colo-
of
a
13. Best, L.
C., Martin, T. J., Russell, R. G. G., Preston, F. E. Nature, 1977, 267, 851. 14. Moncada, S., Higgs, E. A., Vane, J. R. Lancet, 1977, i, 17. 15. Spaet, T. H., Zucker, M. B. Am. J. Physiol. 1964, 206, 1267. 16. Gaarder, A., Jonson, J., Laland, S., Hellem, A., Owren, P. A. Nature, 1961, 192, 531. 17. Charo, I. F., Feinman, R. D, Detwiler, T. C., Smith, J. B., Ingerman, C. H., Silver, M. J. ibid. 1977, 269, 68. 1. Irvin, T. T. CH.M. thesis, University of Aberdeen, 1974. 2. Everett, W. G. Br. J. Surg. 1975, 62, 135. 3. Goligher, J. C., Lee, P. W. G., Simkins, K. C., Lintott, D. J. ibid. 1977, 64, 609.
Serum glucose and calcium levels after S.C.T.
acute
administration of
