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Biomedical subjects

A J McCulloch

Publications and source records attributed to A J McCulloch.

At least 19 recordsLinked to original sources
PubMed2003

Screening for diabetic retinopathy: a cause for concern in people who drive.

AIMS: To report a case of a road traffic accident in a lady driving home from a diabetes clinic after pupillary dilatation. We also present the findings of a questionnaire survey of health professionals to elicit their practice in dealing with such patients. METHODS: We present the case report of a lady having a road traffic accident on her way back from a retinal screening appointment after having had pupillary dilatation. A subsequent postal questionnaire survey was undertaken to find out current practice in screening patients who drive on the day of their retinal screening. RESULTS: A lady was involved in a road traffic accident whilst returning home after retinal screening. Her motor insurance company refused to cover subsequent claims for damage because her pupils had been dilated. She was also prosecuted by the police for driving without valid motor insurance. We conducted a postal survey of 500 health care workers including ophthalmologists, optometrists, diabetologists and general practitioners regarding the use of dilating drops in people with diabetes who intend to drive. Analysis of 320 valid responses confirmed that there is no consistent practice with regard to either the use of dilating drops in drivers or in ensuring that arrangements are made for subsequent adequate visual inspection in those whom dilatory drops are not instilled. CONCLUSIONS: Guidelines, for use by health care professionals and people with diabetes, are clearly required regarding the use of pupillary dilating drops in drivers.

Accidents, Traffic↗
PubMed1986

Glucose turnover in compensated hepatic cirrhosis.

Glucose turnover and recycling from glucose derived 3-carbon intermediates were examined in overnight fasted patients with compensated hepatic cirrhosis and in age- and weight-matched normal control subjects. Fasting blood concentrations of glucose, lactate and glycerol were similar in both groups but blood pyruvate (60 +/- 10 vs. 80 +/- mumol/l, P less than 0.05), blood alanine (0.23 +/- 0.02 vs 0.34 +/- 0.02 mmol/l, P less than 0.01) were decreased and serum insulin increased (19 [13-24]v 7 [4-11] mU/l, P less than 0.01) in cirrhotic subjects. Absolute glucose turnover, assessed by analysis of decay of [3H]-3-glucose specific activity was decreased in cirrhotic patients (8.1 +/- 0.6 v 12.1 +/- 0.7 mol/kg-1 min-1). Glucose "recycling", assessed by the difference between absolute glucose turnover and that given by [14C]-1-glucose data, was normal in cirrhotic patients suggesting that Cori cycle (glucose-lactate-glucose) activity was normal. These data support previous findings of decreased peripheral glucose utilisation and insulin resistance in cirrhotic patients.

Adult↗
PubMed1985

The effect of vasopressin infusion on glucose metabolism in man.

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down glycogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4.9 +/- 0.1 to a peak of 5.7 +/- 0.2 mmol/l (P less than 0.001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3-hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11.19 +/- 0.43 to 13.38 +/- 0.63 mu mol/kg/min (P less than 0.001). Infusion of AVP also increased plasma glucagon concentrations from 38 +/- 8 to 79 +/- 20 pg/l (P less than 0.01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.

Adult↗
PubMed1985

Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis.

The pattern of insulin secretion following an oral glucose load and the insulin receptor status and insulin sensitivity of adipocytes have been studied in patients with thyrotoxicosis and in matched controls. Thyrotoxic subjects showed normal basal and peak levels of serum immunoreactive insulin (peak, 69.0 +/- 6.8 vs 54.3 +/- 8.8 mU/l) and serum C-peptide (peak, 1.95 +/- 0.13 vs 1.71 +/- 0.12 nmol/l for thyrotoxic and control subjects, respectively). Peak serum proinsulin was higher in the thyrotoxic group (64.8 +/- 7.3 vs 39.0 +/- 3.7 pmol/l; P less than 0.01). Maximum specific insulin binding to adipocytes was decreased in the thyrotoxic group (1.80 +/- 0.18 vs 2.62 +/- 0.27%; P less than 0.025) and half-maximum displacement of tracer insulin was similar in the two groups, suggesting that reduced receptor number rather than reduced affinity accounted for the difference. However, adipocyte insulin sensitivity was normal as judged by half-maximal stimulation values of 13.9 +/- 3.6 vs 11.4 +/- 2.1 pmol/l, respectively for lipogenesis and 24.3 +/- 2.2 vs 24.6 +/- 3.6 pmol/l, respectively for glucose transport. Hence, thyroid hormone excess appears to affect adipocyte insulin receptor number directly, but change in receptor number is not associated with change in adipocyte insulin sensitivity in hyperthyroidism. The normal insulin secretion together with the failure to demonstrate abnormal insulin sensitivity of one of the major peripheral tissues suggests that disturbed hepatic rather than peripheral insulin responsiveness may be responsible for the glucose intolerance of hyperthyroidism.

Adipose Tissue↗
PubMed1985

A comparison of 3 methods for assessing insulin sensitivity in subjects with normal and abnormal glucose tolerance.

The euglycaemic clamp, insulin sensitivity test with somatostatin, and insulin sensitivity test without somatostatin, were compared as in vivo methods of assessing insulin sensitivity. Fifteen subjects with varying degrees of glucose tolerance were studied. Somatostatin was not found to influence the assessment of insulin sensitivity by the insulin sensitivity test. When glucose disposal was expressed as metabolic clearance rate significant strong correlations were found between the euglycaemic clamp technique and the insulin sensitivity test with (r = 0.90) and without (r = 0.83) somatostatin. The effects of the tests on intermediary metabolism were also similar, and all 3 tests showed a similar impairment of insulin sensitivity in subjects with abnormal glucose tolerance. The insulin sensitivity test without somatostatin thus provides a simple and economical tool for studying insulin sensitivity.

Adult↗
PubMed1984

Enhanced gluconeogenic capacity from glycerol in hyperthyroid man: evidence in favour of a beta-adrenergic mechanism.

We have previously shown that gluconeogenesis, assessed by glycerol clearance, is increased in hyperthyroid man. The mechanism underlying this change is uncertain but many of the metabolic changes found in hyperthyroidism are thought to be due to increased catecholamine sensitivity of peripheral tissues. To test the hypothesis that enhanced gluconeogenic capacity from glycerol in hyperthyroidism might be mediated via a beta-adrenergic mechanism we have estimated glycerol clearance in thyrotoxic subjects before and during treatment with a non-selective beta-adrenergic blocking drug propranolol (Inderal LA). Control subjects of similar age and weight were also tested. In hyperthyroid subjects, blood glucose and blood glycerol concentrations were increased but blood lactate, pyruvate and alanine concentrations were normal. Glycerol clearance was increased and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three fold. Following beta-blockade blood glucose and blood glycerol concentrations fell although blood glucose concentrations remained above normal values. Glycerol clearance and endogenous glycerol production were also decreased but remained significantly higher than in control subjects. Serum thyroxine and serum triiodothyronine concentrations showed no significant change although mean values fell by 10% and 17% respectively. We conclude that the increase in gluconeogenic capacity from glycerol in hyperthyroid subjects is mediated in part by a beta-adrenergic mechanism.

Adult↗
PubMed1984

Subacute benzodiazepine treatment: observations on behavioural tolerance and withdrawal.

The acute and subchronic actions of the benzodiazepines triazolam, oxazepam and diazepam have been examined using three behavioural tests. In the accelerating rotarod motor coordination test both diazepam and oxazepam on acute administration produced dose-related discoordination or motor impairment in mice. After chronic administration (50 mg/kg per day i.p. for 14 days) the corresponding dose-response lines were shifted to the right suggesting tolerance development. In a test for conflict behaviour in rats (conditioned suppression of drinking) oxazepam (20 mg/kg i.p.), triazolam (1 mg/kg i.p.) and diazepam (10 mg/kg i.p.) all augmented punished responding rates with no effect on unpunished responses and this has been speculated to reflect anxiolytic activity. These initial elevations in punished responding displayed a gradual decline during repeated daily administration over 20 days, there being little alteration in the unpunished response levels. In separate studies, chronic treatment of mice with triazolam in the drinking water over 30 days showed diminished pentylenetetrazol-induced seizure latencies compared to the level of protection afforded by triazolam at the beginning of the schedule. In additional experiments, mice injected daily with triazolam (1 mg/kg i.p. for 14 days) exhibited a higher seizure susceptibility than their corresponding controls. The results are discussed in relation to tolerance to the anxiolytic, anticonvulsant and neurological impairment properties of benzodiazepines.

Animals↗
PubMed1983

Insulin sensitivity in hyperthyroidism: measurement by the glucose clamp technique.

Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

3-Hydroxybutyric Acid↗
PubMed1983

Evidence that thyroid hormones regulate gluconeogenesis from glycerol in man.

We have previously reported that glucose production assessed using radioisotopic methods is 50% increased in hyperthyroidism but 30% decreased in hypothyroidism. These studies, however, do not distinguish between glycogenolysis and gluconeogenesis. In fasting man more than 80% of circulating glycerol is cleared by the liver and enters the gluconeogenic pathway. We have therefore measured glycerol clearance following bolus intravenous glycerol administration as an indirect assessment of gluconeogenic capacity. Hyperthyroid and hypothyroid subjects were compared with separate matched controls after an overnight fast. In hyperthyroid subjects blood glucose and blood glycerol were increased but lactate, pyruvate, and alanine concentrations were normal. Glycerol clearance was increased in hyperthyroidism and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three-fold. In hypothyroidism fasting circulating levels of glucose, lactate, pyruvate, alanine, and glycerol were normal but glycerol clearance was diminished. Both first and second component half-times were prolonged in hypothyroidism and endogenous glycerol production was decreased by 50%. Thus in hyperthyroidism glycerol clearance is greatly enhanced whilst in hypothyroidism glycerol clearance is diminished. The magnitude of the changes suggests that alterations in gluconeogenesis are probably the major factors concerned in the reported increase and decrease in glucose production in hyperthyroidism and hypothyroidism respectively.

Blood Glucose↗
PubMed1983

Circulating somatostatin concentrations in healthy and non-insulin-dependent (type II) diabetic subjects.

A technically simple radioimmunoassay for somatostatin-like immunoreactivity (SLI) in human plasma, which uses polyethylene glycol 6000 to precipitate tracer-degrading enzymes and high molecular weight interfering components, is described and validated. Fasting concentrations of SLI in peripheral plasma were similar in healthy and non-insulin-dependent diabetic (NIDD) subjects (range 3-39 pg/ml) but showed fluctuations for individuals in both groups when sampled frequently over a 60-min period. The mean coefficient of variation of SLI concentration was, however, less (8.0%; range 3-13%) in the diabetic group than in age-matched healthy subjects (19.5%; range 11-44%) (P less than 0.02). Thus the regulation of basal D cell activity or of the somatostatinergic nervous system may be altered in type II diabetic subjects. A hospital breakfast (550 kcal) was a weak stimulus for release of SLI in both healthy and diabetic subjects. The rise in plasma SLI was sustained over 120 min. An increment in plasma SLI over mean basal levels of 5.9 +/- 0.8 pg/ml was observed in young (mean age 23 yr; N = 6) control subjects, 7.9 +/- 2.0 pg/ml in older (mean age 55 yr; N = 7) control subjects and 5.9 +/- 0.6 pg/ml (mean age 62 yr; N = 7) in diabetics. Oral glucose (75 g) produced only a transient and erratic rise in plasma SLI that was not significant at any time point for either healthy or NIDD subjects. It is concluded that further investigations are necessary before hypotheses linking somatostatin deficiency with the hormonal and metabolic abnormalities of non-insulin-dependent diabetes can be accepted.

Adult↗
PubMed1982

Assessment of glucose turnover in normal man with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer.

1. Glucose kinetics were assessed in seven normal adult male subjects by an intravenous bolus technique with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer. Tracer enrichment in plasma was assessed by gas chromatography-mass spectrometry. For comparison five subjects also received a simultaneous intravenous bolus of [6-3H]glucose and kinetics were assessed by conventional means. 2. Administration of [6,6-2H]glucose did not alter circulating glucose or insulin concentrations. 3. Glucose turnover, assessed by the use of [6,6-2H]glucose, was 11.4 (+/- 0.9) micromol min-1 kg-1 and 11.6 (+/- 0.5) micromol min-1 kg-1 with rate of glucose was 2.3 (+/- 0.3) ml min-1 kg-1 with both isotopically labelled tracers. Estimates of mean residence time, glucose pool and glucose space were also similar by each technique. 4. [6,6-2H]Glucose is therefore an effective tracer and allows investigation of glucose kinetics without administration of a radioactive label.

Adult↗