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BILE IN ACUTE CHOLERA
405 tion associated with multiple congenital defects. This seems to be specially indicated when parents have had more than one affected child and/or multiple spontaneous abortions. Such studies may permit identification of persons with presumed balanced chromosomal translocations who probably have an increased risk for having children with unbalanced chromosomal constitutions due to the translocation chromosomes. This finding has obvious importance for genetic counselling. The finding of multiple twins in this family cannot be explained at this time, nor can its relevance to the chromosomal problem be explained. Further studies and
on
this
family will be presented in detail later.
Departments of Medicine, Pediatrics, Psychiatry, U.C.L.A. School of Medicine, Los Angeles, California 90024, and Pacific State Hospital, Pomona California.
ROBERT S. SPARKES ROBERT E. CARREL STANLEY W. WRIGHT.
BILE IN ACUTE CHOLERA
SIR,-A characteristic feature of patients with acute, severe cholera is the opalescent liquid stool called " rice water " because of its lack of colour and the presence of floating bits of mucus. An old clinical adage holds that a change of stool colour to green heralds recovery. Earlier workers speculated that a functional obstruction existed somewhere in the biliary system in acute cholera, but Cole and Greenoughdemon-
Appearance of bile in stool of patient with
severe
cholera after fatty
meal.
strated the patency of the bileducts
by the recovery of sulphoadministered sodium, bromophthalein intravenously, from rice-water stool.
function of the gallbladder-the release of stored passed a tube into the second part of the duodenum of a patient with severe cholera and aspirated rice-water-like fluid. The patient then drank 100 ml. of melted butter and periodic aspirations were made. Immediately after collection and filtration at OOC, bilirubin was measured in the aspirates by the diazo method of Malloy and Evelyn. The results are seen in the accompanying figure. The duodenal-fluid samples became deeply green, the visual intensity corresponding to the rising concentration of bilirubin. The last sample still had a faintly green tint. The previously colourless stool turned green 1-2 hours after the butter meal and gradually returned to a yellowish colour 12 hours later. Since patients often have no appetite for, or are not given, fatty foods early in the course of their illness, the change in stool colour seen later may reflect only increased food intake To test
one
bile-we
(a significant clinical improvement in Pakistan-SEATO Cholera Research Laboratory, Dacca-12, East Pakistan. 1. 2.
Cole, J. Malloy,
many
illnesses).
NORBERT HIRSCHHORN.
R., Greenough, W. B. III. Lancet, 1965, ii, 972. H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481.
SULPHATED INSULIN IN RESISTANT JUVENILE DIABETES SIR,-In 1964, Moloney et al.1 prepared sulphated insulin (S.I.) and showed it to be less antigenic and less neutralisable by antibodies than non-modified insulin. In 1966 Little and Arnott2 compared s.i. with commonly used insulins: they observed that the s.i. greatly reduced the insulin requirement in two patients with insulin-resistant diabetes. It did not differ in its action from the other insulins in other forms of mild or severe diabetes. We report here the good results of using s.i. in a patient with resistant juvenile diabetes. A 13-year-old Israeli girl was referred to us with insulinresistant diabetes. She was normally developed and had regularly menstruated since the age of 12. Her grandmother and the grandmother’s sister were diabetic. The patient had been first admitted to hospital at the age of 10 years, when diabetes was diagnosed and controlled with 24 i.u. protamine zinc insulin (P.Z.I.)+24 i.u. regular insulin (R.i.). Shortly after, her insulin requirements had increased, and she was again admitted, 9 months later, in a precomatous state with acidosis and ketosis. Since increased doses of P.Z.I. and R.I. had not controlled her diabetes, isophane insulin (N.P.H.) was tried. With 100 i.u. N.P.H. and 24 I.U. R.I. fasting bloodglucose levels had oscillated between 180 and 300 mg. per 100 ml., and urinary glucose excretion between 40 and 200 g. per day. Phenformin was added (25 mg. three times daily) and a slight improvement was apparently observed. Some months later she had again been admitted in a precomatose state. She excreted 100-200 g. per day glucose in urine, and the fasting blood-glucose levels oscillated between 250 and 420 mg. per 100 ml. despite progressively increased doses of insulin. It was concluded, clinically only (since insulin antibodies could not be tested), that she was insulin-resistant, and prednisone (’ Meticorten ") was tried together with insulin. Since there was no sufficient clinical improvement, the patient was discharged on 200 i.u. P.Z.I. per day. With this amount of insulin, as well as with much higher doses that were tried, she had excreted 100-200 g. per day glucose in urine and blood-glucose oscillated between 200-300 mg. per 100 ml. She had felt well apart from increased asthenia and severe pruritus vulvae that had developed recently. At this time the patient was referred to us. The glucose curve, after intravenous (sheep) insulin administration (10 i.u.) was completely flat (290 mg. per 100 ml., before insulin, and 292, 295, 282, 283, and 298 mg. per 100 ml., 15, 30, 60, 90, and 120 minutes respectively afterwards). The patient had almost the same flat curve after intravenous administration of 1 g. of tolbutamide. Intravenous administration of pork insulin (10 i.u.) lowered the bloodglucose from 270 to 204 mg. per 100 ml. after 30 minutes, and therefore pork insulin was substituted for the sheep insulin she had been receiving until them. With 50 i.u. pork insulin lente (P.I.L.) and 30 i.u. pork regular insulin, the bloodglucose tested at 12 A.M. and at 5 P.M. oscillated between 100 and 164 mg. per 100 ml. 2 weeks later the blood-glucose rose and, despite increased doses of P.I.L. (200 i.u.), the level varied between 270 and 385 mg. per 100 ml., and urine excretion of glucose varied around 200 g. per day, with acetonuria. Apparently she developed resistance to this insulin also. (Insulin antibodies could not be tested for, because of technical reasons.) We now started giving her s.i., 60 I.U. twice daily, and in the first week her blood-glucose, tested in the morning in the fasting condition, was about 169 mg. per 100 ml., and urinary glucose excretion about 30 g. per 24 hours. She had a hypoglycaemic reaction on the 7th day of this treatment, and we reduced the s.i. to 50 i.u. morning and evening. Blood-glucose levels varied between 159 and 178 mg. per 100 ml., and the urine was free of glucose. 4 months later hypoglycæmic reactions reappeared, and we reduced the S.I. to 40 i.u. morning and evening. 1 month later, after a further hypoglycæmic reaction, we reduced the dose to 30 i.u. mom1. Moloney, P. J., Aprile, M. A., Wilson, S. J. New Drugs, 1964, 4, 258. 2. Little, J. A., Arnott, J. H. Diabetes, 1966, 15, 457.
on
this
family will be presented in detail later.
Departments of Medicine, Pediatrics, Psychiatry, U.C.L.A. School of Medicine, Los Angeles, California 90024, and Pacific State Hospital, Pomona California.
ROBERT S. SPARKES ROBERT E. CARREL STANLEY W. WRIGHT.
BILE IN ACUTE CHOLERA
SIR,-A characteristic feature of patients with acute, severe cholera is the opalescent liquid stool called " rice water " because of its lack of colour and the presence of floating bits of mucus. An old clinical adage holds that a change of stool colour to green heralds recovery. Earlier workers speculated that a functional obstruction existed somewhere in the biliary system in acute cholera, but Cole and Greenoughdemon-
Appearance of bile in stool of patient with
severe
cholera after fatty
meal.
strated the patency of the bileducts
by the recovery of sulphoadministered sodium, bromophthalein intravenously, from rice-water stool.
function of the gallbladder-the release of stored passed a tube into the second part of the duodenum of a patient with severe cholera and aspirated rice-water-like fluid. The patient then drank 100 ml. of melted butter and periodic aspirations were made. Immediately after collection and filtration at OOC, bilirubin was measured in the aspirates by the diazo method of Malloy and Evelyn. The results are seen in the accompanying figure. The duodenal-fluid samples became deeply green, the visual intensity corresponding to the rising concentration of bilirubin. The last sample still had a faintly green tint. The previously colourless stool turned green 1-2 hours after the butter meal and gradually returned to a yellowish colour 12 hours later. Since patients often have no appetite for, or are not given, fatty foods early in the course of their illness, the change in stool colour seen later may reflect only increased food intake To test
one
bile-we
(a significant clinical improvement in Pakistan-SEATO Cholera Research Laboratory, Dacca-12, East Pakistan. 1. 2.
Cole, J. Malloy,
many
illnesses).
NORBERT HIRSCHHORN.
R., Greenough, W. B. III. Lancet, 1965, ii, 972. H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481.
SULPHATED INSULIN IN RESISTANT JUVENILE DIABETES SIR,-In 1964, Moloney et al.1 prepared sulphated insulin (S.I.) and showed it to be less antigenic and less neutralisable by antibodies than non-modified insulin. In 1966 Little and Arnott2 compared s.i. with commonly used insulins: they observed that the s.i. greatly reduced the insulin requirement in two patients with insulin-resistant diabetes. It did not differ in its action from the other insulins in other forms of mild or severe diabetes. We report here the good results of using s.i. in a patient with resistant juvenile diabetes. A 13-year-old Israeli girl was referred to us with insulinresistant diabetes. She was normally developed and had regularly menstruated since the age of 12. Her grandmother and the grandmother’s sister were diabetic. The patient had been first admitted to hospital at the age of 10 years, when diabetes was diagnosed and controlled with 24 i.u. protamine zinc insulin (P.Z.I.)+24 i.u. regular insulin (R.i.). Shortly after, her insulin requirements had increased, and she was again admitted, 9 months later, in a precomatous state with acidosis and ketosis. Since increased doses of P.Z.I. and R.I. had not controlled her diabetes, isophane insulin (N.P.H.) was tried. With 100 i.u. N.P.H. and 24 I.U. R.I. fasting bloodglucose levels had oscillated between 180 and 300 mg. per 100 ml., and urinary glucose excretion between 40 and 200 g. per day. Phenformin was added (25 mg. three times daily) and a slight improvement was apparently observed. Some months later she had again been admitted in a precomatose state. She excreted 100-200 g. per day glucose in urine, and the fasting blood-glucose levels oscillated between 250 and 420 mg. per 100 ml. despite progressively increased doses of insulin. It was concluded, clinically only (since insulin antibodies could not be tested), that she was insulin-resistant, and prednisone (’ Meticorten ") was tried together with insulin. Since there was no sufficient clinical improvement, the patient was discharged on 200 i.u. P.Z.I. per day. With this amount of insulin, as well as with much higher doses that were tried, she had excreted 100-200 g. per day glucose in urine and blood-glucose oscillated between 200-300 mg. per 100 ml. She had felt well apart from increased asthenia and severe pruritus vulvae that had developed recently. At this time the patient was referred to us. The glucose curve, after intravenous (sheep) insulin administration (10 i.u.) was completely flat (290 mg. per 100 ml., before insulin, and 292, 295, 282, 283, and 298 mg. per 100 ml., 15, 30, 60, 90, and 120 minutes respectively afterwards). The patient had almost the same flat curve after intravenous administration of 1 g. of tolbutamide. Intravenous administration of pork insulin (10 i.u.) lowered the bloodglucose from 270 to 204 mg. per 100 ml. after 30 minutes, and therefore pork insulin was substituted for the sheep insulin she had been receiving until them. With 50 i.u. pork insulin lente (P.I.L.) and 30 i.u. pork regular insulin, the bloodglucose tested at 12 A.M. and at 5 P.M. oscillated between 100 and 164 mg. per 100 ml. 2 weeks later the blood-glucose rose and, despite increased doses of P.I.L. (200 i.u.), the level varied between 270 and 385 mg. per 100 ml., and urine excretion of glucose varied around 200 g. per day, with acetonuria. Apparently she developed resistance to this insulin also. (Insulin antibodies could not be tested for, because of technical reasons.) We now started giving her s.i., 60 I.U. twice daily, and in the first week her blood-glucose, tested in the morning in the fasting condition, was about 169 mg. per 100 ml., and urinary glucose excretion about 30 g. per 24 hours. She had a hypoglycaemic reaction on the 7th day of this treatment, and we reduced the s.i. to 50 i.u. morning and evening. Blood-glucose levels varied between 159 and 178 mg. per 100 ml., and the urine was free of glucose. 4 months later hypoglycæmic reactions reappeared, and we reduced the S.I. to 40 i.u. morning and evening. 1 month later, after a further hypoglycæmic reaction, we reduced the dose to 30 i.u. mom1. Moloney, P. J., Aprile, M. A., Wilson, S. J. New Drugs, 1964, 4, 258. 2. Little, J. A., Arnott, J. H. Diabetes, 1966, 15, 457.