- Email: [email protected]
TRANSFER TO INSULIN ZINC SUSPENSION
187 at heart level. In the elevated regions the local pressure falls to a figure where capillary bleeding is so slow that it is no longer troublesome. A local pressure of 35-45 mm. Hg is often necessary for this, especially in highly vascular tissue such as skin and mucosa. On the other hand, experience has shown that 55-65 mm. Hg is the minimum systolic pressure below which it is dangerous and profitless to proceed. This pressure has always been measured at heart level on the arm. At the same time, it was realised that a careful observation of the site of operation, of the nature of the bleeding, its colour, &.c., was as important as the blood-pressure level (Enderby and Pelmore 1951), and it becomes obvious now why the local effect is of even greater significance than the blood-pressure. Thus the local pressure at the site of operation can be reduced below the level where bleeding is troublesome, while at the same time the pressure at heart level is maintained at some figure which experience has shown to be reasonably safe. A systolic pressure of 60 mm. Hg was stated by Dr. John Gillies (personal communication 1949) to be adequate for cellular respiration and metabolism in all vital organs, provided the blood was well oxygenated and that vasodilatation was ensured. From the observations presented here it can be deduced that (1) the local systolic blood-pressure can be considerably lower than 60 mm. Hg, which apparently does not damage the brain ; and (2) in the reversed Trendelenburg position other vital organs are at a pressure somewhat above that of the heart. Gillies’s observations therefore require qualification. A systolic blood-pressure level of 60 mm. Hg at the heart, although adequate for all metabolic requirements when the body is horizontal, is not necessarily so when the body is tilted. Posture may reduce the local bloodpressure in the elevated regions to such an extent that local circulatory requirements cannot be met. However, this is unlikely to cause a dangerously low pressure in any vital organ except the brain, and experience has shown that this organ will tolerate a lower pressure than was at first believed possible. A pressure of at least 60mm. Hg must always be maintained at heart level.
blood:pressure
-
TRANSFER TO INSULIN ZINC SUSPENSION M. G. FITZGERALD M.B. Birm., M.R.C.P. SENIOR REGISTRAR
P. A. THORN M.D.
J. M. MALINS
Lond., M.R.C.P., D.C.H.
M.B. Birm., M.R.C.P.
SENIOR REGISTRAR
ASSISTANT PHYSICIAN
From the Diabetic
Clinic,
General
Hospital, Birmingham
FROM their work on 300 diabetic patients HallasMoller et al. (1952) predicted that 90% of all those needing insulin could be controlled with a single daily injection of one of the insulin zinc preparations elaborated at the Novo Laboratories of Copenhagen. The obvious advantages of ’Insulin Zinc Suspension Lente’ (i.z.s. lente), containing 30% amorphous and 60% crystalline zinc insulin, are the stability of such a mixture ,of a slow and rapid acting insulin, and the freedom from local reactions. Clinical trials of i.z.s. lente in this country have been reported by Lawrence and Oakley (1953), Oakley (1953), Murray and Wilson (19.53), and Nabarro and Stowers (1953a and b). The object of the investigation described here was to determine the effect of transferring patients already receiving insulin to an equivalent dose of i.z.s. lente. As this change often has to be made without admission of the patient to hospital it is important to know whether diabetic control is likely to be altered. Oakley described 15, and Murray and Wilson 21, cases in which this comparison was made ; their results are shown in table i. In most of these patients the standard of initial biochemical control was high. The results shown in table i are impressive in that control of the diabetes was improved in 20 out of a total of 36 cases, and remained the same in 9 others. In only 3 cases was control worse. Methods and Results patients ; 24 were
We havestudied 30 6
Summary Vasomotor control maintains the blood-pressure constant at heart level in the conscious human irrespective
of posture. Elsewhere gravity induces a gradient of arterial pressure when the body is tilted. The elevated regions are reduced in pressure by 30 mm. Hg for every 15 inches of vertical height above heart level. The pressure in dependent regions is raised by a similar amount. This same gradient exists in the anæsthetised patient
were
outpatients
and
inpatients.
Accurate judgment of biochemical control of outpatients is difficult. Therefore, we admitted outpatients for two separate thirty-six-hour periods of assessment on the same days of two successive weeks. While in to bed the and went dressed, hospital patients got up, at their normal times. They were given a day’s work, similar to that of their usual day, and were allowed to leave the hospital to take exercise. They took meals at TABLE
I-RESULT
TRANSFER FROM OTHER I.Z.S. IN SAME DOSE
OF
INSULINS
TO
after autonomic paralysis with hexamethonium. For adequate control of surgical haemorrhage it may be necessary to reduce the blood-pressure at the site of
operation to 35-45 mm. Hg. This constitutes the essential
feature of "postural ischsemia." A pressure of at least 60mm. Hg-must always be maintained at heart level. *
In a reversed Trendelenburg position of about 30°-35° the cerebral blood-pressure is estimated at 35-40 mm. Hg when the heart pressure is 60 mm. Hg. Other vital organs are at a pressure higher than that at heart level. REFERENCES
Best, C. H., Taylor,
N. B. (1945) The Physiological Basis of Medical Practice. London. Enderby, G. E. H. (1950) Lancet, i, 1145. Pelmore, J. F. (1951) Ibid, i, 663. —
Hill, L. (1909) Heart, 1, 73. Flack, M., (1909) Brit.
med. J. i, 272. C. F. (1948) J. clin. Invest. 27, 476. Loman, J., Dameshek, W., Myerson, A., Goldman, D. (1936) Arch. Neurol. Psychiat., Chicago, 35, 1216. Shackleton, R. P. W. (1951) Brit. med. J. i, 1054. —
Kety, S. S., Schmidt,
*
Murray and Wilson state no conclusions, but the figures given show that i.z.s. has had the stronger insulin action throughout the day.
188 their usual time, and the total dietary carbohydrate was the same on both occasions. During the first stay they took their usual insulin, and on the day of discharge they had i.z.s. They then returned to work, taking i.z.s. each day and were readmitted after they had been on i.z.s. for six days. On each occasion the assessment of control began at 8 A.M. on the day after admission. Two-hourly blood-sugar estimations were done over twenty-four hours, and twelve-hour
specimens urine
TABLE III=SUMMARY OF RESULTS OF TRANSFER FROM OTHER
INSUISNS TO I.Z.S.
of
were
patient who was on a high ratio of s.i./p.z.i. was alone in being worse on transfer to i.z.s. It seems reasonable to suppose that some patients who need an s.l.jP.z.I. mixture in higher proportions than 2 :1 will need a higher proportion of’I.Z.S. Amorphous’ than is con-
collected from 8 A.M. to 8P.M. and 8 P.M. to 8 A.M.
The
patients
in-
tained in
i.z.s. lente. of the cases which had been treated with a mixture of s.i. and P.Z.I. in proportions of less than 2 : 1, or in equal proportions, showed a close similarity in the shape of their twenty-four-hour blood-sugar curves
were
Many
assessed in the same way.
The results
(see fig. 2).
of these tests are shown in table 11. The results are
Of the 4
summarised in table 111. Discussion
Fig. I-Case 28 (woman, aged 39). two
doses of 5.1.
Transfer from Poor initial biochemical control.
Table III shows that control was
unchanged
cases
in this group which
we
classed
as
better,
9 and 11 were both well controlled before admission (see table II), but case 9 produced high figures on both test days and case 11 on her first test day. This suggests that admission to hospital upset the control of these 2 patients and throws doubt on the conclusion that their condition was improved by transfer to i.z.s.
cases
DEGREE OF CONTROL
in
In figs. 1-3 the numbers enclosed in circles over half and indicate glycosuria expressed as grammes per worse in a 12 hours (8 a.m. to 8 p.m. and 8 p.m. to third, on 8 a.m.). Ration = 10 g. of carbohydrate.
transfer to This is i.z.s.
in contrast with the improvement reported in the majority by other workers (see table i). We think that two factors may explain this difference-the initial type of insulin and the degree of control. TYPE OF INSULIN
Transfer from Soluble Insulin Alone (see fig. 1) Of 8 patients whom we transferred from two doses of soluble insulin (S.I.) 4 developed severe diabetic symptoms (cases 26-29). This deterioration of control on transfer of patients from two doses of s.i. to a longeracting insulin has often been reported, and precautions are usually taken to avoid it. i.z.s. provides no exception to this rule.
Another difference between our series and those we have quoted in table i is that in 10 of our patients initial clinical control of the diabetes was poor. Furthermore, in the 17 with good clinical control the blood-sugar levels were mostly higher than those reported by Oakley (1953) and Murray and Wilson (1953). This indicates poor biochemical control; and most of our cases were selected for this reason. Those who were both clinically and biochemically well controlled before transfer (cases 6, 9, 11, 23-25) remained satisfactory after transfer, but generally speaking transfer to i.z.s. is more likely to be considered in those who are not well controlled. Our results suggest that the transfer of cases with indifferent biochemical control to an equal dose of i.z.s. lente is likelier to produce deterioration than improvement. An increase in the total dose of insulin will often be required at the time of transfer. This is certainly so with patients who have been on two doses of
This deterioration did not occur in the three inpatients whom we transferred from s.i. alone (cases 23-
25).
Transfer froni, Mixtures of S.I. and P.Z.I. The transfer in this group caused little disturbance except in cases 18 and 21. Case 17 was much
biochemically, but patient did not develop symptoms. These 3 pati-
worse
the
each having a S.I./P.Z.I. mixture in a In 2 :1 or higher ratio. Oaldey’s series the only
ents
Fig. 3-Case 6 (man, aged 33).
were
Transfer from S.1.1 Good initial biochemical control. Subsequently 2 rations were transferred from breakfast to lunch and I to tea, with return to excellent control.
P.Z.1. mixture.
Fig. 2-Case 13 (woman, aged 27). Transfer from
S.I./P.Z.I. control.
mixture.
Poor
initial
biochemical
189
DATA
OF 30 CASES TREATED
WITH (A)
SOLUBLE INSULIN, PROTAMINE ZINC AND SUBSEQUENTLY WITH (B) INSULIN ZINC SUSPENSION
INSULIN, OR GLOBIN INSULIN, ,
’ These agates are the mean of the last six estimationa made at routine outpatient visits. -The specimens were taken in the early inpatient. afternoon, after the midday meal. LP. good clinical control had for the last year been free from thirst, polyuria, and pruritus ; they felt well, Patients classed as having had a steady weight, and did not have frequent hypoglyoacmia. D = diabetic symptoms. H hypoglyceemia. =
=
We have described patients 50
when either they developed diabetic symptoms which were not present before, or the mean bloodWe have described patients as better when the mean blood-sugar level and the sugar level rose by ’ maximum vajiation both fell. Ketosis developed after two days. the dose of i.z.s. had to be increased. tSKttfciymptoms as worse
mg. or more per 100 ml.
developed, and
190 soluble insulin, and probably so when the proportion of S.l. to P.Z.I. is high. In this latter group the proportion of
amorphous to i.z.s. crystalline may need to be changed. Our experience with outpatients not included
i.z.s.
in this series has confirmed these views. In patients with strict biochemical control the distribution of dietary carbohydrate is likely to need alteration at the time of transfer; less carbohydrate will be required at breakfast and more at lunch and tea (see fig. 3). When biochemical control is poor, alteration of the diet is less urgent but is likely to be necessary later.
Summary Of 30 cases of diabetes mellitus transferred from another form of insulin to an equal dose of insulin zinc suspension lente, a third were less well controlled, while in half the control was unchanged. Transfer to insulin zinc suspension lente from other insulin is not free of risk. We wish to thank Dr. P. W. S. Blake and Dr. P. R. Knight for their help with the nocturnal blood-sugar estimations; Dr. R. Gaddie and Mr. Garfield Thomas for the biochemical results and helpful criticism ; and others who have helped in various ways. Generous supplies of insulin were provided by Evans Medical Supplies and Burroughs Wellcome & Co.
mixture is described in thisway it is difficult to calculate the exact dose of each type of insulin which is being ordered. i.z.s. lente is a mixture of known percentage : 30% of i.z.s. (A) and 70% of i.z.s. (c) ; therefore it seems logical that one should think of other mixtures in the same terms. With the aid of a graph (see figure) the amount of each type of insulin in a given dose of i.z.s. lente can be seen ; the exact dose of each type of insulin in mixtures of different percentages is also clear. It is then simple to calculate how much i.z.s. (A) or i.z.s. (c) should be added to a dose of i.z.s. lente to make mixtures The prescriber will then know of other percentages. the number of units of each type of insulin which he is ordering. I am most grateful graph.
—
—
PRESCRIBING INSULIN ZINC SUSPENSION MIXTURES M.D.
P. A. THORN Lond., M.R.C.P., D.C.H. SENIOR REGISTRAR
From the Diabetic
Clinic, General Hospital, Birmingham
IN the treatment of diabetic patients with insulin zinc suspension it is likely that various proportions ofI.Z.S. Amorphous’ (I.z.s. [A]) andI.Z.S. Crystalline’ (i.z.s. [c]) will be required. In previous reports (Nabarro and Stowers (1953a and b)) and in the manufacturers’ literature it is suggested that mixtures of the two should be prescribed as a given proportion of ’I.Z.S. Lente ’ to one of its two ingredients (1:1, 2 : 1, &c.). When the
Mr. T. F. Dee for
reproducing
the
REFERENCES
Nabarro, J. D. N., Stowers, J. M. (1953a) Proc. R. Soc. Med. 46, 864. (1953b) Brit. med. J. ii, 1027. —
—
A FATAL CASE OF
SODIUM NITRITE POISONING G. M. G. BARTON
REFERENCES
Hallas-Møller, K., Jersild, M., Peterson, K., Schlichtkrull, J. (1952) First Congress of the International Diabetes Federation. Leyden. Lawrence, R. D., Oakley, W. (1953) Brit. med. J. i, 242. Murray, I., Wilson, R. B. (1953) Ibid, ii, 1023. Nabarro, J. D. N., Stowers, J. M. (1953a) Proc. R. Soc. Med. 46, 864. (1953b) Brit. med. J. 1953, ii, 1027. Oakley, W. (1953) Ibid, p. 1021.
to
B.Sc., M.B. Lond. ASSISTANT PATHOLOGIST SALISBURY
THE
HOSPITALS,
WILTS.
cases of fatal sodium nitrite that I have been able to trace are those of a family of two adults and a child (McQuiston 1936). Sodium nitrite was found in the salt-cellar and basin of cooking-salt, and was isolated from the stomach contents of the three patients and from remnants of the meal. It was not established how sodium nitrite came to be in the salt, but one of the victims had access to this substance at work. Oppe (1951) describes a case in which a fatal outcome was prevented in a baby aged 2 months by giving intravenous methylene-blue. The baby had sodium nitrite 2 added to its feed of sodium citrate. instead gr. In the following case death occurred about three hours after taking sodium nitrite.
only previous
poisoning
A boy, aged 2 years, vomited while playing with his elder brother. After vomiting a second time he was given a glass of water and made to lie on the bed. The elder brother then produced an almost empty open bottle of sodium nitrite which the child had been licking. The child vomited once or twice On admission he was deeply more and was taken to hospital. cyanosed, collapsed, and crying with spasms of pain. His stomach was washed out, and administered, but his condition oxygen remained unchanged for three-quarters of an hour, after which he had a spasm and died.
Necropsy Findings.—The body was that of a well-developed cyanosed child. The mouth and oesophagus were normal, but the gastric mucosa was slightly inflamed. In spite of the vomiting and gastric lavage, the stomach contained a considerable amount of undigested food. The blood was darker than usual. The other organs were normal. 6-15 mg. of sodium nitrite was obtained from the stomach washings and 0-15 mg. from the stomach contents (Ilosvay’s reaction) Vomited material was not available for Nitric oxide haemoglobin was analysis. shown to be present in the blood by spectroscopy and by the colour reaction after boiling (Lucas 1935). The sodium nitrite had been bought Graph showing number of units of insulin in varying percentages of the total dose of I.Z.S.
chemist’s
at
shop by the child’s elder brother, aged 9, who wanted it for a chemical experiment about which he had a
blood:pressure
-
TRANSFER TO INSULIN ZINC SUSPENSION M. G. FITZGERALD M.B. Birm., M.R.C.P. SENIOR REGISTRAR
P. A. THORN M.D.
J. M. MALINS
Lond., M.R.C.P., D.C.H.
M.B. Birm., M.R.C.P.
SENIOR REGISTRAR
ASSISTANT PHYSICIAN
From the Diabetic
Clinic,
General
Hospital, Birmingham
FROM their work on 300 diabetic patients HallasMoller et al. (1952) predicted that 90% of all those needing insulin could be controlled with a single daily injection of one of the insulin zinc preparations elaborated at the Novo Laboratories of Copenhagen. The obvious advantages of ’Insulin Zinc Suspension Lente’ (i.z.s. lente), containing 30% amorphous and 60% crystalline zinc insulin, are the stability of such a mixture ,of a slow and rapid acting insulin, and the freedom from local reactions. Clinical trials of i.z.s. lente in this country have been reported by Lawrence and Oakley (1953), Oakley (1953), Murray and Wilson (19.53), and Nabarro and Stowers (1953a and b). The object of the investigation described here was to determine the effect of transferring patients already receiving insulin to an equivalent dose of i.z.s. lente. As this change often has to be made without admission of the patient to hospital it is important to know whether diabetic control is likely to be altered. Oakley described 15, and Murray and Wilson 21, cases in which this comparison was made ; their results are shown in table i. In most of these patients the standard of initial biochemical control was high. The results shown in table i are impressive in that control of the diabetes was improved in 20 out of a total of 36 cases, and remained the same in 9 others. In only 3 cases was control worse. Methods and Results patients ; 24 were
We havestudied 30 6
Summary Vasomotor control maintains the blood-pressure constant at heart level in the conscious human irrespective
of posture. Elsewhere gravity induces a gradient of arterial pressure when the body is tilted. The elevated regions are reduced in pressure by 30 mm. Hg for every 15 inches of vertical height above heart level. The pressure in dependent regions is raised by a similar amount. This same gradient exists in the anæsthetised patient
were
outpatients
and
inpatients.
Accurate judgment of biochemical control of outpatients is difficult. Therefore, we admitted outpatients for two separate thirty-six-hour periods of assessment on the same days of two successive weeks. While in to bed the and went dressed, hospital patients got up, at their normal times. They were given a day’s work, similar to that of their usual day, and were allowed to leave the hospital to take exercise. They took meals at TABLE
I-RESULT
TRANSFER FROM OTHER I.Z.S. IN SAME DOSE
OF
INSULINS
TO
after autonomic paralysis with hexamethonium. For adequate control of surgical haemorrhage it may be necessary to reduce the blood-pressure at the site of
operation to 35-45 mm. Hg. This constitutes the essential
feature of "postural ischsemia." A pressure of at least 60mm. Hg-must always be maintained at heart level. *
In a reversed Trendelenburg position of about 30°-35° the cerebral blood-pressure is estimated at 35-40 mm. Hg when the heart pressure is 60 mm. Hg. Other vital organs are at a pressure higher than that at heart level. REFERENCES
Best, C. H., Taylor,
N. B. (1945) The Physiological Basis of Medical Practice. London. Enderby, G. E. H. (1950) Lancet, i, 1145. Pelmore, J. F. (1951) Ibid, i, 663. —
Hill, L. (1909) Heart, 1, 73. Flack, M., (1909) Brit.
med. J. i, 272. C. F. (1948) J. clin. Invest. 27, 476. Loman, J., Dameshek, W., Myerson, A., Goldman, D. (1936) Arch. Neurol. Psychiat., Chicago, 35, 1216. Shackleton, R. P. W. (1951) Brit. med. J. i, 1054. —
Kety, S. S., Schmidt,
*
Murray and Wilson state no conclusions, but the figures given show that i.z.s. has had the stronger insulin action throughout the day.
188 their usual time, and the total dietary carbohydrate was the same on both occasions. During the first stay they took their usual insulin, and on the day of discharge they had i.z.s. They then returned to work, taking i.z.s. each day and were readmitted after they had been on i.z.s. for six days. On each occasion the assessment of control began at 8 A.M. on the day after admission. Two-hourly blood-sugar estimations were done over twenty-four hours, and twelve-hour
specimens urine
TABLE III=SUMMARY OF RESULTS OF TRANSFER FROM OTHER
INSUISNS TO I.Z.S.
of
were
patient who was on a high ratio of s.i./p.z.i. was alone in being worse on transfer to i.z.s. It seems reasonable to suppose that some patients who need an s.l.jP.z.I. mixture in higher proportions than 2 :1 will need a higher proportion of’I.Z.S. Amorphous’ than is con-
collected from 8 A.M. to 8P.M. and 8 P.M. to 8 A.M.
The
patients
in-
tained in
i.z.s. lente. of the cases which had been treated with a mixture of s.i. and P.Z.I. in proportions of less than 2 : 1, or in equal proportions, showed a close similarity in the shape of their twenty-four-hour blood-sugar curves
were
Many
assessed in the same way.
The results
(see fig. 2).
of these tests are shown in table 11. The results are
Of the 4
summarised in table 111. Discussion
Fig. I-Case 28 (woman, aged 39). two
doses of 5.1.
Transfer from Poor initial biochemical control.
Table III shows that control was
unchanged
cases
in this group which
we
classed
as
better,
9 and 11 were both well controlled before admission (see table II), but case 9 produced high figures on both test days and case 11 on her first test day. This suggests that admission to hospital upset the control of these 2 patients and throws doubt on the conclusion that their condition was improved by transfer to i.z.s.
cases
DEGREE OF CONTROL
in
In figs. 1-3 the numbers enclosed in circles over half and indicate glycosuria expressed as grammes per worse in a 12 hours (8 a.m. to 8 p.m. and 8 p.m. to third, on 8 a.m.). Ration = 10 g. of carbohydrate.
transfer to This is i.z.s.
in contrast with the improvement reported in the majority by other workers (see table i). We think that two factors may explain this difference-the initial type of insulin and the degree of control. TYPE OF INSULIN
Transfer from Soluble Insulin Alone (see fig. 1) Of 8 patients whom we transferred from two doses of soluble insulin (S.I.) 4 developed severe diabetic symptoms (cases 26-29). This deterioration of control on transfer of patients from two doses of s.i. to a longeracting insulin has often been reported, and precautions are usually taken to avoid it. i.z.s. provides no exception to this rule.
Another difference between our series and those we have quoted in table i is that in 10 of our patients initial clinical control of the diabetes was poor. Furthermore, in the 17 with good clinical control the blood-sugar levels were mostly higher than those reported by Oakley (1953) and Murray and Wilson (1953). This indicates poor biochemical control; and most of our cases were selected for this reason. Those who were both clinically and biochemically well controlled before transfer (cases 6, 9, 11, 23-25) remained satisfactory after transfer, but generally speaking transfer to i.z.s. is more likely to be considered in those who are not well controlled. Our results suggest that the transfer of cases with indifferent biochemical control to an equal dose of i.z.s. lente is likelier to produce deterioration than improvement. An increase in the total dose of insulin will often be required at the time of transfer. This is certainly so with patients who have been on two doses of
This deterioration did not occur in the three inpatients whom we transferred from s.i. alone (cases 23-
25).
Transfer froni, Mixtures of S.I. and P.Z.I. The transfer in this group caused little disturbance except in cases 18 and 21. Case 17 was much
biochemically, but patient did not develop symptoms. These 3 pati-
worse
the
each having a S.I./P.Z.I. mixture in a In 2 :1 or higher ratio. Oaldey’s series the only
ents
Fig. 3-Case 6 (man, aged 33).
were
Transfer from S.1.1 Good initial biochemical control. Subsequently 2 rations were transferred from breakfast to lunch and I to tea, with return to excellent control.
P.Z.1. mixture.
Fig. 2-Case 13 (woman, aged 27). Transfer from
S.I./P.Z.I. control.
mixture.
Poor
initial
biochemical
189
DATA
OF 30 CASES TREATED
WITH (A)
SOLUBLE INSULIN, PROTAMINE ZINC AND SUBSEQUENTLY WITH (B) INSULIN ZINC SUSPENSION
INSULIN, OR GLOBIN INSULIN, ,
’ These agates are the mean of the last six estimationa made at routine outpatient visits. -The specimens were taken in the early inpatient. afternoon, after the midday meal. LP. good clinical control had for the last year been free from thirst, polyuria, and pruritus ; they felt well, Patients classed as having had a steady weight, and did not have frequent hypoglyoacmia. D = diabetic symptoms. H hypoglyceemia. =
=
We have described patients 50
when either they developed diabetic symptoms which were not present before, or the mean bloodWe have described patients as better when the mean blood-sugar level and the sugar level rose by ’ maximum vajiation both fell. Ketosis developed after two days. the dose of i.z.s. had to be increased. tSKttfciymptoms as worse
mg. or more per 100 ml.
developed, and
190 soluble insulin, and probably so when the proportion of S.l. to P.Z.I. is high. In this latter group the proportion of
amorphous to i.z.s. crystalline may need to be changed. Our experience with outpatients not included
i.z.s.
in this series has confirmed these views. In patients with strict biochemical control the distribution of dietary carbohydrate is likely to need alteration at the time of transfer; less carbohydrate will be required at breakfast and more at lunch and tea (see fig. 3). When biochemical control is poor, alteration of the diet is less urgent but is likely to be necessary later.
Summary Of 30 cases of diabetes mellitus transferred from another form of insulin to an equal dose of insulin zinc suspension lente, a third were less well controlled, while in half the control was unchanged. Transfer to insulin zinc suspension lente from other insulin is not free of risk. We wish to thank Dr. P. W. S. Blake and Dr. P. R. Knight for their help with the nocturnal blood-sugar estimations; Dr. R. Gaddie and Mr. Garfield Thomas for the biochemical results and helpful criticism ; and others who have helped in various ways. Generous supplies of insulin were provided by Evans Medical Supplies and Burroughs Wellcome & Co.
mixture is described in thisway it is difficult to calculate the exact dose of each type of insulin which is being ordered. i.z.s. lente is a mixture of known percentage : 30% of i.z.s. (A) and 70% of i.z.s. (c) ; therefore it seems logical that one should think of other mixtures in the same terms. With the aid of a graph (see figure) the amount of each type of insulin in a given dose of i.z.s. lente can be seen ; the exact dose of each type of insulin in mixtures of different percentages is also clear. It is then simple to calculate how much i.z.s. (A) or i.z.s. (c) should be added to a dose of i.z.s. lente to make mixtures The prescriber will then know of other percentages. the number of units of each type of insulin which he is ordering. I am most grateful graph.
—
—
PRESCRIBING INSULIN ZINC SUSPENSION MIXTURES M.D.
P. A. THORN Lond., M.R.C.P., D.C.H. SENIOR REGISTRAR
From the Diabetic
Clinic, General Hospital, Birmingham
IN the treatment of diabetic patients with insulin zinc suspension it is likely that various proportions ofI.Z.S. Amorphous’ (I.z.s. [A]) andI.Z.S. Crystalline’ (i.z.s. [c]) will be required. In previous reports (Nabarro and Stowers (1953a and b)) and in the manufacturers’ literature it is suggested that mixtures of the two should be prescribed as a given proportion of ’I.Z.S. Lente ’ to one of its two ingredients (1:1, 2 : 1, &c.). When the
Mr. T. F. Dee for
reproducing
the
REFERENCES
Nabarro, J. D. N., Stowers, J. M. (1953a) Proc. R. Soc. Med. 46, 864. (1953b) Brit. med. J. ii, 1027. —
—
A FATAL CASE OF
SODIUM NITRITE POISONING G. M. G. BARTON
REFERENCES
Hallas-Møller, K., Jersild, M., Peterson, K., Schlichtkrull, J. (1952) First Congress of the International Diabetes Federation. Leyden. Lawrence, R. D., Oakley, W. (1953) Brit. med. J. i, 242. Murray, I., Wilson, R. B. (1953) Ibid, ii, 1023. Nabarro, J. D. N., Stowers, J. M. (1953a) Proc. R. Soc. Med. 46, 864. (1953b) Brit. med. J. 1953, ii, 1027. Oakley, W. (1953) Ibid, p. 1021.
to
B.Sc., M.B. Lond. ASSISTANT PATHOLOGIST SALISBURY
THE
HOSPITALS,
WILTS.
cases of fatal sodium nitrite that I have been able to trace are those of a family of two adults and a child (McQuiston 1936). Sodium nitrite was found in the salt-cellar and basin of cooking-salt, and was isolated from the stomach contents of the three patients and from remnants of the meal. It was not established how sodium nitrite came to be in the salt, but one of the victims had access to this substance at work. Oppe (1951) describes a case in which a fatal outcome was prevented in a baby aged 2 months by giving intravenous methylene-blue. The baby had sodium nitrite 2 added to its feed of sodium citrate. instead gr. In the following case death occurred about three hours after taking sodium nitrite.
only previous
poisoning
A boy, aged 2 years, vomited while playing with his elder brother. After vomiting a second time he was given a glass of water and made to lie on the bed. The elder brother then produced an almost empty open bottle of sodium nitrite which the child had been licking. The child vomited once or twice On admission he was deeply more and was taken to hospital. cyanosed, collapsed, and crying with spasms of pain. His stomach was washed out, and administered, but his condition oxygen remained unchanged for three-quarters of an hour, after which he had a spasm and died.
Necropsy Findings.—The body was that of a well-developed cyanosed child. The mouth and oesophagus were normal, but the gastric mucosa was slightly inflamed. In spite of the vomiting and gastric lavage, the stomach contained a considerable amount of undigested food. The blood was darker than usual. The other organs were normal. 6-15 mg. of sodium nitrite was obtained from the stomach washings and 0-15 mg. from the stomach contents (Ilosvay’s reaction) Vomited material was not available for Nitric oxide haemoglobin was analysis. shown to be present in the blood by spectroscopy and by the colour reaction after boiling (Lucas 1935). The sodium nitrite had been bought Graph showing number of units of insulin in varying percentages of the total dose of I.Z.S.
chemist’s
at
shop by the child’s elder brother, aged 9, who wanted it for a chemical experiment about which he had a