T. Russell Fraser

BREATH-ACETONE AND BLOOD-SUGAR MEASUREMENTS IN DIABETES

Abstract The concentration of breath acetone has been found to correlate with the β-hydroxybutyrate concentration of venous blood in fasting obese patients. Overnight fasting levels of both breath acetone and blood-sugar were measured in 251 diabetics, after which the patients were grouped for analysis by the type of diabetic management and the fasting blood-sugar found. Amongst the subgroups with near-normal fasting blood-sugar ( 100 g. carbohydrate per day); it was raised in similarly well-controlled patients receiving either reducing diets (

Bladder dysfunction and neuropathy in diabetes

SummaryEstablished urodynamic and electrophysiological techniques have been applied to assess the frequency and extent of autonomic and peripheral neuropathy in 60 subjects with diabetes mellitus; 38 were diabetics with suggestive symptoms and the others were representative newly diagnosed (11) or treated (11) diabetics. Objective evidence of neuropathic bladder dysfunction was detected in 43 of them (71.7%). The commonest abnormality was a hypotonic, insensitive large capacity bladder, which condition was usually asymptomatic. Less frequently (15%) this was complicated by bladder decompensation and sphincter involvement, resulting in excessive residual urine and infection; some of these had bladder paralysis with chronic painless retention of urine (7%). Electrophysiological studies found a sensory defect in the lower limbs in all tested patients (100%), and in 41 patients (69%) an associated motor conduction abnormality, which was more frequent and marked in the lower than the upper limb. These functional abnormalities appeared to be related to the severity of diabetes, but less to its duration. Indeed of 11 newly diagnosed diabetics tested 7 had a peripheral neuropathy and 4 urodynamic abnormalities. The high incidence of bladder dysfunction and peripheral neuropathy in this series indicates the frequency of subclinical diabetic neuropathy and a factor needing more emphasis in diabetic uropathy.

SERUM-GROWTH HORMONE AND GLUCOSE INTOLERANCE IN RENAL FAILURE

Abstract Serum-growth-hormone (G.H.) measurements during oral glucose-tolerance tests were done on forty-one patients with chronic renal failure, seven patients with nephrotic syndrome, and fifty controls. Of the patients with chronic renal failure, 54% had impaired glucose tolerance (2-hour blood-sugar greater than 120 mg. per 100 ml.) and G.H. levels were raised in 49%, but not significantly among those with impaired glucose tolerance. In chronic renal failure, the Serum-G.H. level correlated directly with the serum creatinine and inversely with serum-albumin. It is suggested that protein malnutrition may be an important factor determining the raised levels of G.H. in renal failure.

TRIGLYCERIDE METABOLISM IN THYROID DISEASE

Abstract The fasting levels of plasma-triglyceride were increased in nine out of ten primary hypothyroid subjects, and they returned towards normal after thyroxine therapy. In seven thyrotoxic patients, fasting triglyceride levels were low normal and the mean levels did not change after antithyroid therapy. The clearance-rate of an infused triglyceride load showed abnormalities more striking than the changes observed in circulating triglyceride level. The clearance-rate in hypothyroid subjects was low and in the thyrotoxic patients it was either high or normal. After treatment of either state the fractional clearance-rates tended towards normal. There were parallel changes in free-fatty-acid flux. In the hypothyroid subjects, a slow clearance of exogenous triglyceride was associated with low post-heparin lipolytic activity (P.H.L.A.), but in the thyrotoxic subjects the rapid clearance of triglyceride was associated with unexpected low or low normal P.H.L.A. levels. It is suggested that in thyroid disease the tissue clearance of circulating triglycerides may be an important determinant of fasting plasma-triglyceride values.

STIMULATION TESTS OF PITUITARY-LEYDIG CELL FUNCTION IN NORMAL MALE SUBJECTS AND HYPOGONADAL MEN

The Leydig cell reserve was assessed by measuring plasma 17 ß‐hydroxy androgens (17 OHA) after two injections of human chorionic gonadotrophin (HCG) 2000 i.u. 3 days apart. In fifteen normal men the 17 OHA rose by a mean of 109%, to above 11 ng/ml, between 1 and 3 days after intramuscular injection. In cryptorchid boys the response was much slower, adult levels being reached in 1‐4 weeks. In panhypopituitarism 17 OHA levels rose rapidly to the normal range, whereas in isolated gonadotrophin deficiency the response was much more variable. Subjects with chromatin‐positive Klinefelters syndrome also responded to HCG. No response was seen in patients with complete testicular degeneration. Peak serum HCG levels occurred at 24 hr.

Production and storage of [125I] thyroxine and [125I] triiodothyronine of high specific activity

High specific activity [125-I] triiodothyronine and [125-I] thyroxine have been produced regularly by the chloramine T radioiodination method. Simultaneous production of [125-I] triiodothyronine and [125-I] thyroxine is usual when diiodothyronine or triiodothyronine are employed as the starting materials. Specific activities reached vary with the starting compound (diiodothyronine, triiodothyronine, thyroxine) used, as both substitution and, less readily, exchange of iodine atoms take place. Starting with diiodothyronine specific activities of approximately 2400 and 5200 Ci/g were achieved for [125-I]triidothyronine and [125I] thyroxine, respectively, and, similarly, specific activities of approximately 1200 and 4000 Ci/g for [125I] triiodothyronine and [125I]-thyroxine, respectively, were reached when triiodothyronine was the starting material. [125-I] Triiodoacetic acid and [125I] tetraiodoacetic acid have been produced in the same way from triiodoacetic acid. By column chromatography on Sephadex G-25 (fine), eluting with alkaline phosphate buffer, good separation of the radioiodinated products has been readily achieved. Studies on the stability of the radioiodinated hormones showed that 50% methanol, ethanol, propanol and propylene glycol were all equivalent as preserving agents and, further, that the stability of the radioiodinated hormones was linearly related to the concentration of these preserving agents.

MEASUREMENT OF THYROXINE AND TRIIODOTHYRONINE IN HUMAN URINE

Abstract Urinary excretion of unconjugated Summary thyroxine (T 4 ) was 2·0 μg. per day (mean) in thirty-six normal subjects. The renal clearance of serum unbound T4 was 26 ml. per minute (mean) in ten subjects. Hydrolysis of conjugated T4 in urine, however, yielded a further 2·8 μg. per day (mean) by enzyme hydrolysis or 3·7 μg. per day by acid hydrolysis. Mean figures for percentages of unconjugated and conjugated thyroxine were 39% and 61% of total T4, respectively. The unconjugated fraction should reflect the prevailing serum level of unbound T4, and be a useful thyroid-function test. Urinary immunoassayable triiodothyronine (T3) was 0·8 μg. per day (mean) in thirty-eight normal subjects. This fraction was 52% (mean) of the total T3, which was no more than 1·4 μg. per day (mean), in nine subjects. It is probably close to the amount of unconjugated T3. Renal clearance of serum unbound T3 seemed to be greater than glomerular filtration-rate in some cases, raising the possibility of tubular excretion of T3.

Stimulation by insulin of the incorporation of U14C-glucose into lipids released by the liver

SummaryIn a new incubation system, liver slices from rat have been shown to incorporate glucose into lipids, which are released into the incubation medium. This synthesis was stimulated by insulin with a proportionally more marked increase in esterified fatty acids than in free fatty acids.

SERUM INSULIN, GLUCOSE, AND LIPID LEVELS AMONG MILD DIABETICS IN RELATION TO INCIDENCE OF VASCULAR COMPLICATIONS

Abstract One hundred and seventeen non-insulin-requiring diabetics attending a diabetic clinic have been studied with respect to vascular complications, lipid levels, and glucose and insulin response after oral glucose. There was an inverse correlation between blood-sugar and insulin levels at 60 minutes, the regression line of which was used to divide the patients into those with moderate and those with poor insulin responses. The vascular complications were not associated with raised levels of serum triglyceride or cholesterol, but there were more complications among those with a poor insulin response than among those with a moderate insulin response. Those with a poor insulin response had lower triglyceride levels than those with a moderate insulin response.

THE EFFECT OF YTTRIUM-90 IMPLANTATION ON ENDOCRINE FUNCTION AND VISUAL FIELDS IN PATIENTS WITH ‘FUNCTIONLESS’ PITUITARY TUMOURS, WITH BIOPSY AND RADIOLOGICAL FINDINGS

Thirty patients with symptoms from ‘functionless’ * pituitary tumours were treated by yttrium‐90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62.5%, and reduced in 12.5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre‐implant.