PubMed Health⌕ Search

Biomedical subjects

J M Burrin

Publications and source records attributed to J M Burrin.

At least 145 records · Page 8Linked to original sources
PubMed1985

The physiological and pharmacological role of presynaptic alpha- and beta-adrenoceptors in man.

Two studies were performed each in six normal volunteers in order to find evidence of either a physiological or pharmacological role of presynaptic alpha- and presynaptic beta-adrenoceptors in man. In Study 1 subjects received a 60 min infusion of guanfacine 3 mg (alpha 2-adrenoceptor agonist) preceded by either idazoxan (alpha 2-adrenoceptor antagonist) or vehicle. Guanfacine reduced plasma noradrenaline concentration by approximately 30% and this fall was not antagonised by the alpha 2-receptor antagonist. The 30-fold increase in plasma growth hormone, measured as a marker of the central action of guanfacine, was almost completely blocked by idazoxan. A comparison of the drug concentrations of idazoxan and guanfacine, together with their relative affinities for alpha 2-adrenoceptors, suggested that the idazoxan could not block the peripheral actions of guanfacine and that these were responsible for the fall in plasma noradrenaline concentration. In Study 2 adrenaline 0.05 micrograms kg-1 min-1 was infused for 80 min preceded by either idazoxan or vehicle. After vehicle, adrenaline caused no change in plasma noradrenaline concentration whereas it rose approximately 25% after administration of idazoxan. This was probably due to unmasking of presynaptic beta-adrenoceptor stimulation by adrenaline when the opposing inhibitory autoreceptor was blocked.

Adrenergic beta-Antagonists↗
PubMed1985

Performance of a quality-assessment scheme for blood glucose meters in general practice.

We describe our experience with a quality-assessment scheme for Glucometer users in General Practice based on simultaneous blood samples taken on filter paper strips and posted to the laboratory. The accuracy of results from these blood glucose meters outside the laboratory was below generally accepted laboratory standards; 30% of results fell outside +/- 20% of the laboratory value. Only 58% of the filter paper strips sent out were returned for analysis, suggesting a lack of awareness of the benefits and importance of such a scheme by the G.P. Glucometer users.

Blood Glucose↗
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. The Central Biochemistry Laboratory in the Multicenter Kroc Study. Problems and proposals.

The advantages of a multicenter trial can easily be lost if results from individual centers cannot be safely combined for statistical analysis. One objective of the Kroc Study was to develop methods that would allow valid amalgamation of results from laboratories at the six clinical centers and a central biochemical laboratory at the University of Newcastle upon Tyne. Responsibilities of the local laboratories, in addition to measurement of plasma glucose, creatinine, and glycosylated hemoglobin, were to obtain and prepare samples for measurement of plasma glucose, glycosylated hemoglobin, and serum lipids at the central laboratory, of C-peptide at the University of Chicago, and to collect and prepare samples for measurement of urinary albumin excretion at Guy's Hospital. The central laboratory was additionally to provide a system to ensure the comparability of plasma glucose determinations between and within centers, and to advise on common procedures for sample handling. Major problems were encountered with sample labeling, dispatch, and transport to the central laboratory. Although central determinations of plasma glucose and serum lipids were still possible in transported specimens, central assay of glycosylated hemoglobin proved inaccurate and useless. Compliance with the plasma glucose quality control program was variable among centers. Although the difference between the centers recording the highest and lowest values was 24.6% of the mean estimate of plasma glucose level, correlation between local and central plasma glucose determinations was good (r = 0.99, see pages 22-26).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1984

Mechanisms of catecholamine effects on ketogenesis.

Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.

Animals↗
PubMed1984

Performance of three enzymic methods for filter paper glucose determination.

Collection of blood spots on filter paper offers a practical alternative for home monitoring of diabetic patients. We have compared the merits of three protein precipitants, trichloracetic acid (TCA), perchloric acid (PCA) and sulphosalicylic acid (SSA) for the elution of glucose from the filter paper, and their subsequent effects on three enzymic methods, glucose dehydrogenase (GDH), hexokinase (HK), and glucose oxidase (GOD) for the determination of glucose using a microcentrifugal analyser. The combination of TCA elutant with the GDH method was superior with respect to time course of reaction and elution time from the filter paper, and was chosen for routine use. Within- and between-batch precision for this method was 2.7% and 3.2% respectively at normal glucose concentrations. Recovery of glucose added to whole blood was 110 +/- 5%. Comparison with an automated glucose oxidase method for plasma glucose gave a slope of 1.1, intercept of -0.7 and a correlation coefficient of 0.9 (n = 64). We conclude that the combination of TCA and glucose dehydrogenase provides a robust, precise and accurate method for the quantitation of glucose in filter-paper blood spots. The procedure offers increased sensitivity and better precision than GOD methods. The use of TCA as elutant gives a faster elution time and has the least effect on any of the enzymic methods.

Blood Glucose↗
PubMed1983

A collaborative study of the measurement of glycosylated haemoglobin by several methods in seven laboratories in the United Kingdom.

A collaborative study compared methods for measuring glycosylated haemoglobin in seven laboratories in the United Kingdom. No satisfactory standard for general use was found. Satisfactory internal quality control systems were in use for each assay which allowed the maintenance of a normal range in each participating laboratory. No satisfactory quality control system suitable for general use could be identified. Costs and convenience of the assays are reported. The technical problems with each type of assay and precautions for their use were identified, such as the need for standardization in incubation times, the practicability of automation of colorimetric assays, and the precision of pH needed for buffers in column separation methods. The relevance of the technical problems to interpretation of measurements is also considered. It is concluded that laboratories measuring glycosylated haemoglobin should maintain a normal range, use 'in-house' quality controls to monitor assay performance and keep clinical colleagues informed of the findings and of any changes in methodology that might affect the interpretation of results.

Autoanalysis↗
PubMed1983

Carbohydrate and lipid metabolism during continuous ambulatory peritoneal dialysis (CAPD): the effect of a single dialysis cycle.

The effect on hormonal status and intermediary metabolism of a single 6 h dialysis cycle at two different concentrations of dialysate glucose was investigated in six patients on continuous ambulatory peritoneal dialysis. The basal blood glucose level was elevated by 0.5 mmol/l, associated with a threefold increase in basal serum insulin compared with seven normal controls. Blood glucose and serum insulin rose further during dialysis, particularly with hypertonic (215 mmol of glucose/l) dialysis fluid and levels remained high for 6 h after the onset. Plasma glucagon concentrations were 2.7-fold increased and did not decrease to normal during dialysis. Concentrations of the gluconeogenic precursors lactate and alanine were consistently raised, and levels of circulating non-esterified fatty acids and ketone bodies were lowered, particularly with hypertonic dialysis fluid. The long-term effects of sustained hyperinsulinaemia, including suppression of lipolysis and ketogenesis, require further investigation.

Adult↗
PubMed1983

Dopamine blockade inhibits starvation ketosis in man.

The effects of dopamine blockade on the endocrine and metabolic response to starvation have been investigated by administration of metoclopramide, 30 mg daily, or placebo to five normal subjects fasted for sixty hours on two occasions. Blood glucose and alanine concentrations fell with starvation and metoclopramide had no further effect. Concentrations of the other gluconeogenic precursors, lactate and pyruvate, were also unaffected by metoclopramide. The rise in circulating ketone body concentrations with fasting was impaired by metoclopramide, significantly from 44 h onwards (blood total ketone body concentration at 60 h, 3.42 +/- 0.94 mmol/l with placebo; 2.08 +/- 0.67 mmol/l with metoclopramide, P less than 0.05). Blood glycerol and plasma non-esterified fatty acids (NEFA) levels rose with starvation, and metoclopramide had no further effect. Serum insulin concentrations remained low with fasting, while circulating glucagon and growth hormone levels rose. Similar changes were noted with both metoclopramide and placebo. Serum prolactin concentrations during starvation were elevated two to four fold by metoclopramide. The inhibitory effect of dopamine blockade on ketosis thus occurred despite hyperprolactinaemia, and did not result from measurable alterations in insulin, glucagon or growth hormone secretion. The data suggest a stimulatory role for endogenous dopamine on starvation ketonaemia in man.

Acidosis↗
PubMed1982

Intensive attention improves glycaemic control in insulin-dependent diabetes without further advantage from home blood glucose monitoring: results of a controlled trial.

Forty-six diabetics treated with twice-daily insulin were seen every two weeks for six months in an intensive education programme aided by regular home urine glucose testing. Control was improved with a decrease in 24-hour urinary glucose excretion (median 138 mmol/24 h (24.8 g/24 h) falling to 70 mmol/24 h (12.6 g/24 h); p less than 0.002), glycosylated haemoglobin concentration (mean 11.4 +/- SD 2.3% falling to 10.4 +/- 1.5%; p less than 0.001), and Diastix score (median 3.0 falling to 1.3; p less than 0.001). There was no reported increase in hypoglycaemia. Thirty-eight of the diabetics proceeded to a nine-month randomised cross-over study of the effect on blood glucose control of monitoring urinary glucose or blood glucose measured visually or by a reflectance meter using appropriate reagent strips. No further improvement in control was observed after home blood glucose monitoring. Nevertheless, 29 out of 37 patients preferred blood to urine glucose monitoring. During both the education and cross-over studies there was evidence of an initial improvement in control followed by deterioration. This was independent of the monitoring method used in the cross-over period and may have been due to waning enthusiasm. Despite patient enthusiasm and other reports to the contrary, home blood glucose monitoring offered no improvement in control over intensive attention and conventional urine glucose monitoring.

Adolescent↗
PubMed1982

Some hormonal influences on glucose and ketone body metabolism in normal human subjects.

Control of glucose and ketone body metabolism is integrated by a variety of hormones. Insulin is the major anabolic hormone, and its actions are antagonized by rapidly acting catabolic hormones, such as glucagon and the catecholamines, and by others such as cortisol, growth hormone and the thyroid hormones, which generally have more delayed effects. In the normal human subject, the effects of catabolic hormones to raise blood glucose are limited by a compensatory increase in insulin secretion, and these effects are enhanced in insulin deficiency. Hyperketonaemic actions of the catabolic hormones may result from increased supply of non-esterified fatty acids from lipolysis, although glucagon has a major direct action to increase ketogenesis at the liver. As expected, these actions are also restricted in normal humans by the compensatory rise in insulin secretion. Hyperketonaemia does, however, occur with adrenaline (epinephrine) and noradrenaline (norepinephrine), even in the presence of mildly elevated insulin concentrations. These catecholamines may assume particular importance in mobilization of lipid fuels in milder forms of stress, when insulin secretion is normal or mildly increased. In severe stress, when there is catecholamine-induced suppression in insulin secretion, lipolytic and hyperketonaemic effects of all the catabolic hormones may be manifest. Starvation in humans also results in diminished insulin secretion and increased catabolic hormone secretion. The relative importance of individual hormones in lipid mobilization during starvation is uncertain, although glucagon, growth hormone, noradrenaline and, possibly, dopamine may all play a part.

3-Hydroxybutyric Acid↗
PubMed1982

Transient triiodothyronine deficiency. Absence of effect on basal or adrenaline-stimulated carbohydrate and lipid metabolism in man.

Severe stress is accompanied by a fall in circulating triiodothyronine levels as well as increases in secretion of several hormones including adrenaline. The present study was designed to test the hypothesis that the fall in triiodothyronine may counteract in part the catabolic effects of stress hormones such as adrenaline. Transient hypothyroidism was induced by administration orally of sodium ipodate (3 g). Adrenaline infusions (6 micrograms/min for 2 hours) were performed in five healthy men before and four days after ipodate was given. Circulating triiodothyronine levels decreased from 1.7 +/- 0.1 to 1.1 +/- 0.1 nmol/l (p less than 0.001), associated with a small rise in serum thyroxine, but basal circulating concentrations of glucose, the gluconeogenic precursors, NEFA and 3-hydroxybutyrate were unaltered. Circulating insulin, glucagon and growth hormone concentrations were also similar with and without prior ipodate ingestion. Adrenaline infusion produced a rise in blood glucose (4.9 +/- 0.2 to 8.5 +/- 0.4 mmol/l at 60 min), lactate, pyruvate and the lactate: pyruvate ratio, which was unaltered by ipodate. Blood glycerol (0.04 +/- 0.004 to 0.13 +/- 0.03 mmol/l at 30 min), plasma NEFA (0.52 +/- 0.05 to 1.31 +/- 0.17 mmol/l at 30 min) and blood 3-hydroxybutyrate concentrations (0.04 +/- 0.004 to 0.26 +/- 0.07 mmol/l at 50 min) were elevated by adrenaline, with similar responses obtained after ipodate. Ipodate also did not influence the circulating insulin and glucagon response to adrenaline infusion. A transient decrease in circulating triiodothyronine concentrations induced by ipodate does not modulate the hormonal and metabolic response to adrenaline in normal man.

3-Hydroxybutyric Acid↗
PubMed1981

Comparative study of subcutaneous, intramuscular, and intravenous administration of human insulin.

Human insulin derived from porcine insulin was given subcutaneously (s.c.), intramuscularly (i.m.), and intravenously (i.v.) to normal men. The dosage for all three routes was 0 . 075 IU/kg body weight. Diluting medium was administered by s.c. injection to obtain control values. Somatostatin (100 microgram/h) was given to inhibit pancreatic beta cell secretion. The plasma glucose responses to s.c. injection of this insulin into the anterior abdominal wall and to i.m. injection into the thigh were similar with respect to the extent, onset, and duration of effect. Plasma glucose fell from mean (+/- SE) pre-injection values of 4 . 3 +/- 0 . 15 and 4 . 4 +/- 0 . 27 mmol/l, to 3 . 06 +/- 0 . 25 and 2 . 98 +/- 0 . 16 mmol/l by 90 to 105 min for s.c. and i.m. studies, respectively, thereafter returning to mean basal level by 6 h after i.m. injection, but remaining about 0 . 5 mmol/l below basal level after s.c. injection. A much more sudden, but short-lived, hypoglycaemic response occurred after i.v. insulin, with plasma glucose failing from 4. 50 +/- 0 . 42 to 1 . 45 +/- 0 . 16 mmol/l by 25 min, returning to mean basal value after 3 1/2 h. The mean (+/- SE) peak insulin levels after s.c. and i.m. injection were 0 . 13 +/- 0 . 01 and 0 . 18 +/- 0 . 04 pmol/ml at 90 and 60 min, respectively. After i.v. injection the maximum plasma insulin concentration of 6 . 9 +/- 0 . 73 pmol/ml was seen at 2 min. No adverse side-effects were observed.

Adult↗
PubMed1981

Human insulin: study of safety and efficacy in man.

The safety and efficacy of a new highly purified neutral soluble human insulin produced by conversion of porcine insulin was compared with a highly purified neutral soluble porcine insulin in six normal men. The insulins were administered by subcutaneous injection at a dose of 0.075 U/kg body weight. Somatostatin was infused during the experiment to suppress endogenous insulin secretin. No difference was found in the plasma glucose, insulin, or metabolite responses. Thus the potency, onset, and duration of effect were identical with the two insulins. No short-term side effects to either insulin were observed. Highly purified, semi-synthetic human insulin offers a safe and effective means to explore the possible advantages of homologous human insulin in the management of diabetes mellitus.

Adult↗
PubMed1981

Dopaminergic control of ketogenesis in fasting.

The role of dopamine in starvation ketonaemia was investigated in male Wistar rats by administration of a specific dopamine receptor antagonist, metoclopramide (4 mg . kg-1 . 24h-1), or placebo, intragastrically during a 48-h fast. Starvation alone caused a fall in blood glucose and gluconeogenic precursor concentrations, which was unaffected by metoclopramide administration. Circulating 3-hydroxybutyrate and acetoacetate levels rose with fasting alone but metoclopramide impaired this ketonaemic response. After 48-h starvation, total ketone body concentrations (mean +/- SEM) were 2.28 +/- 0.19 mmol/l with metoclopramide therapy, 3.49 +/- 0.21 mmol/l with placebo, P less than 0.001. Plasma non-esterified fatty acid levels were similar in metoclopramide- and placebo-treated animals, as were circulating concentrations of insulin, glucagon and growth hormone. Metoclopramide thus decreased the ketonaemic response to starvation without an apparent change in lipolysis or circulating hormone levels, suggesting a direct role for dopamine in production of starvation ketonaemia.

Animals↗
PubMed1981

Diurnal hormone-metabolite profiles in hypothyroidism.

To investigate the influence of thyroid hormones on intermediary metabolism in man, hormone and metabolite profiles were obtained over a 12-h period of normal meals and activity in eight hypothyroid subjects before and during thyroxine replacement therapy, and in sixteen matched controls. The fasting blood glucose concentration and the mean 12-h blood glucose concentration were normal in hypothyroid subjects but the blood glucose response to breakfast was exaggerated. Fasting blood lactate and pyruvate levels were normal but post-prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1.80 +/- 0.06 v. control 0.77 +/- 0.03 mmol/l, P less than 0.01) and pyruvate (0.10 +/- 0.01 v. 0.08 +/- 0.003 mmol/l, P less than 0.01) were elevated. Blood alanine concentrations were elevated only in the evening. Although plasma non-esterified fatty acid levels were normal, fasting blood glycerol levels were decreased (0.06 +/- 0.01 v 0.08 +/- 0.01 mmol/l, P less than 0.001) and this decrease persisted throughout the 12-h period. Blood total ketone body concentrations did not differ from controls, but, as for plasma NEFA and blood glycerol, the normal preprandial rise in concentration was absent. Serum insulin, glucagon and growth hormone concentrations did not differ from control values at any time. Six months of thyroxine (T4) treatment produced a rise in blood glycerol concentration (mean 12 h value during T4 therapy, 0.06 +/- 0.01; before T4 therapy, 0.04 +/- 0.005 mmol/l; P less than 0.01) but not to control values (0.08 +/- 0.01 mmol/l). Concentrations of glucose and other gluconeogenic precursors were unaltered by therapy but the insulin response to meals and the mean 12 h serum insulin concentration were increased.

Acetoacetates↗