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Biomedical subjects

T R Fraser

Publications and source records attributed to T R Fraser.

At least 19 recordsLinked to original sources
PubMed1989

The response to treatment with pituitary growth hormone: the New Zealand experience.

Ninety-four growth hormone deficient New Zealand children were treated with thrice weekly intramuscular injections of human pituitary growth hormone (GH) from 1979 to 1985 and the results from 43 children were analysed in detail. Their height velocity was mean (SD) 4.0 (1.9) cm/yr immediately prior to treatment and 8.5 (3.1) cm/yr in the first year of treatment. In each of the first three years of treatment the height velocity was significantly increased (p less than 0.001), but there was a significant decline in height velocity between the first and second, and second and third years. Nevertheless each year of treatment gave a highly significant gain in relative height. Bone age did not advance more rapidly than chronological age during the first two years of treatment, but did so subsequently. The response to GH, as assessed by the increase in relative height, was negatively correlated with the relative height at the start of treatment and with the maximum pretreatment plasma GH response to insulin hypoglycaemia. There was no correlation with pretreatment relative height velocity or aetiology of GH deficiency. Height velocity improved in five of 14 children treated with thyroxine after starting GH. Discontinuation of GH for one year in 34 children resulted in a highly significant reduction in growth rate from 7.5 (2.4) cm/yr to 2.5 (2.0) cm/yr, however four prepubertal children continued to grow at a rate exceeding 4 cm/yr.

Age Determination by Skeleton↗
PubMed1987

Radiological assessment of Paget's disease of bone after treatment with the bisphosphonates EHDP and APD.

The effects of therapy on the osteolytic bone lesions of Paget's disease have been assessed from serial bone radiographs. Changes in the rate of progression of lytic "wedge" lesions were measured and alterations in the texture of lytic "blade" lesions were graded on an empirical scale. Useful matching was possible using standard radiographs, although special care was needed to avoid artefacts from suboptimal positioning, magnification and variation in exposure. Serial radiographs were obtained of 57 lytic blade lesions in 54 patients receiving treatment with the bisphosphonate 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP) and of 20 lesions in 20 patients treated with oral or intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD). Treatment with EHDP was associated with a significant deterioration in bone texture in 50% of lytic blade lesions, and with healing in only 20%. Deterioration was accompanied by an increase in local bone pain in 17% of these patients. In contrast, significant healing was observed in 17 of 20 lytic lesions (eight wedge, nine blade) within 6 months of beginning a course of intravenous or oral APD. In four of eight patients the progression of a lytic tibial wedge was arrested and in the remaining four the direction of wedge movement was reversed. In two patients the wedge had almost completely "filled in", making measurement difficult. Bone healing was usually accompanied by pain relief, reduction in skin temperature and rapid suppression of the urine hydroxyproline (uHP) into the normal range. However, in four patients who received intravenous APD, repair of lytic bone lesions was observed despite persisting elevation of uHP. These improvements with APD were sustained at 12 months, although in one patient whose biochemical indices were restored to normal the resorption front showed further progression, despite initial temporary reversal. The trends apparent in these short-term studies were also seen in four patients in whom wedge velocities were measured over periods of 6-10 years. These results confirm that after treatment of Paget's disease, bone healing or deterioration can be accurately assessed from serial standard radiographs. Reproducible matching is best achieved by ensuring that all radiographs are taken by the same radiographer. Minor alterations in radiological bone texture provide an important index of drug effect which is not always apparent from measurement of biochemical and other indices.

Aged↗
PubMed1986

Low serum osteocalcin levels in glucocorticoid-treated asthmatics.

Serum osteocalcin (OC) levels were measured in 19 asthmatic patients receiving long term glucocorticoid therapy and in age- and sex-matched asthmatic patients not receiving this treatment. In the glucocorticoid-treated patients, the mean OC level was approximately 50% less than that in the control group (P less than 0.001), and there was a direct correlation between serum OC and 1,25-dihydroxyvitamin D [1,25-(OH)2D; r = 0.71; P less than 0.001]. Multiple regression analysis in a total of 39 glucocorticoid-treated patients indicated that OC correlated directly to 1,25-(OH)2D and inversely to glucocorticoid dose. There was no correlation between OC and 1,25-(OH)2D in the control group and no significant difference in mean serum 1,25-(OH)2D between the steroid-treated asthmatic patients and the asthmatic control patients. The effect of a 4-day course of oral 1,25-(OH)2D on serum OC was studied in six patients with glucocorticoid excess and six normal subjects. There was a similar percent increase in OC levels in both groups, though the basal concentrations and absolute increases were substantially less in the steroid-treated group. It is likely that the depression of serum OC in glucocorticoid-treated patients results from the reduction in the rate of bone formation induced by these hormones.

Administration, Oral↗
PubMed1979

Renal handling of homologous radioiodinated thyrotrophin in the rat.

Previously, TSH metabolism and tissue distribution in the rat were studied using heterologous hormone and/or unphysiological doses. We injected iv [131I]rTSH (S.A. 100 micronCi/microgram) in physiological doses (10 ng) to KI blocked male rats. Two to 180 min after which TCA precipitable 131I was measured in the kidney, liver, muscle, fat and testis. The highest TCA precipitable radioactivity concentration, peak value 12% at 30 min; organ/blood ratio, 16, was found in the kidney. With the kidney validated as the major site of localization of TSH, the renal localization and handling of [125I]rTSH was studied by autoradiography. Radioactivity was confined to the cortex. Two to 30 min samples showed 125I in Bowman's space and luminal parts of the proximal tubular cells while samples from 60 to 180 min revealed activity in contraluminal areas, suggesting glomerular filtration and tubular re-absorption. Gel-filtration of supernatants of kidney homogenates revealed progressive diminution of the TSH peak and the appearance of a smaller MW peak. We conclude that (1) the kidney is the major site of localization and metabolism of homologous TSH, (2) the renal handling of TSH involves both glomerular filtration and tubular re-absorption.

Animals↗
PubMed1976

Effects of methyldopa on prolactin and growth hormone.

The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal.

Adult↗
PubMed1976

Bladder dysfunction and neuropathy in diabetes.

Established 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 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 freuqently (15%) was this 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%) as 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.

Adult↗
PubMed1976

Measurement of an index of muscle capillary permeability and its correlation with serum insulin values in maturity-onset diabetic subjects.

1. An index of capillary permeability was obtained by measuring the ratio of the clearance rate of 77Br to that of 133Xe in the anterior tibial muscle, after a short period of maximal ischaemic exercise. 2. Seventeen control subjects and thirty-two maturity-onset, non-insulin-treated diabetic subjects, aged 60 years or less, were studied. Short glucose tolerance tests were performed in the diabetic subjects during which blood sugar and serum insulin concentrations were estimated. 3. The 77Br/133Xe clearance ratio was increased in the diabetic subjects compared with the control subjects. In the diabetic subjects, there was an inverse correlation between the insulin at 60 min after glucose and the 77Br/133Xe clearance ratio. There was also a direct correlation between the 77Br/133Xe clearance ratio and the age of the patient in the diabetic group but not in the control group. 4. The results demonstrate that a reduced insulin response to oral glucose is associated with increased capillary permability and may play a role in the development of microangiopathy.

Adult↗
PubMed1976

Effects of insulin and procaine hydrochloride on glycogen synthetase activation and adipocyte calcium flux: evidence for a role of calcium in insulin activation of glycogen synthetase.

Observations that insulin-induced stimulation of glycogen synthetase occurs without detectable reduction in cyclic AMP suggests an alternative controlling mechanism. The hypothesis that this stimulation might be mediated through calcium was tested using procaine HC1, a drug whose insulin-like action is not associated with reduction in basal or adrenaline-stimulated cyclic AMP levels. Pretreatment of adipose tissue with insulin or porcaine for 30 minutes increased homogenate glucose-6-phosphate independent ("I") form activity to 58% and 48% respectively with no significant change in total activity. Insulin and procaine also had similar effects on calcium efflux from isolated rat adipocytes. Following an initial displacement of calcium from the adipocytes by insulin (but not by procaine) both agents decreased efflux of calcium, measured following 10, 20 and 30 minutes incubation. In adipose tissue homogenates increasing the free calcium concentration from 10(-8) to 10(-3) M increased "I" form glycogen synthetase activity without significantly altering total activity. A complex interrelationship with ATP and calcium was also observed. In the presence of ATP 0.5 mM maximal activation occurred at 10(-6) M calcium concentration. These findings suggest that insulin-induced activation of glycogen synthetase may be effected by alteration of intracellular free calcium with consequent effects on glycogen synthetase-related enzymes in a mechanism independent of or complementary to effects on cyclic AMP levels.

Adipose Tissue↗
PubMed1976

Oestrogen induced hypertriglyceridaemia: role of the adrenal cortex.

The role of the adrenal cortex in the pathogenesis of hypertriglyceridaemia associated with the intake of oral contraceptive agents containing oestrogen has been investigated in rats. Bilateral adrenalectomy reduced the activity of hepatic enzymes regulating lipogenesis (acetyl CoA carboxylase, fatty acid synthetase) and decreased plasma triglyceride concentrations. On the other hand, the administration of high dosage corticosterone induced the activity of hepatic enzymes with consequent elevation in serum triglyceride levels. In animals with intact adrenals the administration of oestradiol: (a) raised plasma triglyceride levels, (b) enhanced the activity of hepatic enzymes, and (c) increased the adrenal cortex:body weight ratio. The effects (a) and (b) were not observed when both adrenals were removed prior to oestrogen therapy. High dosage corticosterone replacement was found to be essential for the oestradiol to produce its effects on hepatic enzymes and plasma triglyceride levels. The results suggest a regulatory role for the adrenal cortex in the homeostasis of plasma triglyceride concentration and that the hypertriglyceridaemia induced by the oestrogen containing preparations might be secondary to alterations in adrenocortical function.

Acetyl-CoA Carboxylase↗
PubMed1976

Infusions of hFSH and hLH in normal men. I. Kinetics of human follicle stimulating hormone.

Serial serum assays of immunoreactive FSH before, during and after a 4 h intravenous infusion of human follicle stimulating hormone (hFSH) in five healthy men revealed two disappearance rate constants with corresponding mean half-lives of 2.9 and 50.6 h. The mean distribution spaces calculated for the fast and slow component were 4.36 1 and 75.9 1 respectively. The average value for the metabolic clearance rate was 17.2 ml/min and for the endogenous production rate 50.9 mU/min. Two of the subjects had human luteinizing hormone (hLH) added in the infusions without the FSH kinetics changing.

Adult↗
PubMed1976

Infusions of hFSH and hLH in normal men. II. Serum testosterone response to infused hLH and hFSH.

Standardized 4 h intravenous infusions of human follicle stimulating hormone (hFSH) and/or human luteinizing hormone (hLH) were given either separately or combined to 7 normal male volunteers. The infusions raised the serum gonadotrophin levels at least 10 (FSH) and 18 (LH) times above the basal ones. Serum testosterone (T) levels were measured serially before, during and after the infusions and, in 4 subjects, during a corresponding period of another normal day. During a normal or basal 24 h period fluctuations were seen and also a circadian rhythm with lower levels in the evening. The infusion of hFSH alone (3 subjects) did not alter the serum T levels. The infusion of hLH alone in 2 subjects raised serum T levels by 17% and 55% over those of the basal day. The combined FSH/LH infusion caused a significant rise (35-68%) in 4 subjects and greater rise in 2 of them than after infusion of the hLH alone. The serum T responses were gradual, reaching a maximum 7-8 h after the end of the infusion.

Adult↗
PubMed1976

Florid diabetic retinopathy and its response to treatment by photocoagulation or pituitary ablation.

A group of 34 patients with florid diabetic retinopathy are reported. Nine of these had at least one eye untreated and of these only two maintained vision at one year-the others were blind. Ten patients had 11 florid eyes treated by photocoagulation. At one year six were blind and five had good vision. At two years only three could still see. Of 20 pituitary-ablated patients with 29 florid eyes, only three were blind at one year. Even at five years, 12 of 17 eyes could see and only two patients were blind. The one- and two-year visual acuities were significantly better in the pituitary ablated eyes than in the untreated and photocoagulated ones (p = 0.01-0.03). It is suggested that for this rare form of retinopathy pituitary ablation remains the treatment of choice if vision is to be maintained.

Adult↗
PubMed1976

Drug controlled of Cushing's syndrome. Combined aminoglutethimide and metyrapone therapy.

Eighteen patients with Cushing's syndrome (16 pituitary-dependent Cushing's disease, 1 ectopic ACTH syndrome, 1 primary adrenal adenoma) were given a combination of aminoglutethimide and metyrapone, with the object of controlling cortisol overproduction using less toxic doses than would be required with each drug alone. A preliminary trial of this combination using doses of aminoglutethimide of 1 g or more a day was assessed over 2 weeks. Control of cortisol overproduction and clinical improvement was achieved but side effects led to withdrawal of the drugs in 6 out of the 12 patients. A lower dose trial of this combination over 2 weeks, using 750 mg/day of aminoglutethimide also controlled cortisol overproduction and side effects led to drug withdrawal in only 2 out of 6 patients. Four of these patients were successfully controlled with even lower doses (500-750 mg/day of aminoglutethimide) for longer periods (26 days-1 year). This low regimen which consists of aminoglutethimide 500-750 mg daily, metyrapone 2 g daily, dexamethasone 0.5 mg b.d. and fludrocortisone 0.1 mg daily, is useful for preparing patients for operative treatments and may be used as a long-term treatment of milder cases.

Adrenocorticotropic Hormone↗
PubMed1975

The role of calcium in insulin action. III. Calcium distribution in fat cells; its kinetics and the effects of adrenaline, insulin and procaine-HCl.

The effects of adrenaline, insulin and procaine-HCl on Ca distribution in intact fat cells and on Ca binding to fat cell ghost membranes have been investigated. 1. Fat cells incubated in 45Ca containing media till isotopic equilibrium indicated that the exchangeable Ca in these cells averages 25.7 +/-3.2nmol/mg protein, which represents approximately 9.8% of their ttotal Ca content. 2. Perifusion of 45Ca prelabelled fat cells gave washout curves whose analysis conformed with three kinetically distinct Ca pools (Fig. 1). The fast exchangeable pool (Compartment A) had an efflux rate constant of 0.193 +/-0. 013 min.-. The release of Ca from the second and thrid pools (Compartments B and C) was much slower with efflux rate constants of 0.032 +/-0.0018 min.-1 and 0.0042 +/- 0.0006 min.-1 respectively. Changing the Ca concentration in the perifusing medium modified the initial fast phase and its rate constant, while added dinitrophenol (DNP) inhibited the efflux rate from the later compartments...

Adipose Tissue↗
PubMed1975

The role of calcium in insulin action. IV. Mechanism of insulin resistance in adipose tissue of obese (ob/ob) mice and old Wistar rats.

The in-vitro antilipolytic response to insulin and procaine hydrochloride by adipose tissue from young rats (150 - 180 g) and lean mice has been compared with that from aged Wistar rats (600 g) and obese (ob/ob) hyperglycaemic mice. 1. The adipose tissue from the obese mice showed diminished responsiveness to insulin and to procaine hydrochloride. Response to these agents, however, was restored by prewashing the tissue, suggesting that the apparent resistance in this tissue reflected saturation of the insulin receptors to endogenous insulin. 2. In adipose tissue of old Wistar rats the antilipolytic effect of insulin was also impaired, but this was not restored after extensive washing. Unlike adipose tissue ghosts prepared from young rats, insulin did not decrease the binding of calcium to ghost membrane preparations from old rats. Neither did insulin inhibit the adrenaline stimulated 45 calcium efflux from perifused isolated fat cells prepared from old rats. These results suggest that the insulin response of fat cells from old rats is impaired because of a defect either in their insulin receptors or in their post-receptor responses. 3. Procaine-hydrochloride, however, when added to the medium perifusing fat cells of these old rats inhibited the adrenaline stimulated lipolysis, reduced the Ca efflux and decreased the binding of Ca to fat cell ghosts; as it did with similar preparations of young rats. Thus the cells from old rats still show full post-receptor responsiveness to an insulin-like stimulus, provided the stimulus for such a response is given at a point beyond the insulin receptor itself. The results suggest that the insulin resistance observed in old rat fat cells may be related to some by deficiency in the insulin receptors, possibly due to their lower replacement with age.

Adipose Tissue↗
PubMed1975

Production and storage of (125-I) thyroxine and (125-I) 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.

Chromatography, Gel↗