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Biomedical subjects

J M Burrin

Publications and source records attributed to J M Burrin.

At least 109 records · Page 6Linked to original sources

Extra-laboratory blood glucose measurement: a policy statement.

The introduction of test strips for measurement of blood glucose has led to their widespread use by medical and paramedical staff outside the central laboratory. While many users have developed ad hoc schemes of training and quality control, formal guidelines have not been presented. This paper makes recommendations on various aspects of extra-laboratory blood glucose measurement in hospitals, but not in the home, with the aim of improving the safety and reliability of results. It is recommended that: 1. a formal programme of training should be devised by staff in the laboratory together with those in the diabetes service and others as appropriate; 2. laboratory and diabetes staff should train, assess, and approve more senior users who would then take responsibility for the training and performance of more junior colleagues; 3. all users should demonstrate their competence at regular intervals; 4. there should be a quality assurance programme arranged by the laboratory which tests the performance of the operator and the equipment; 5. laboratory staff, in consultation with users, should be responsible for the selection and purchase of equipment; 6. equipment should be cleaned and maintained on a regular basis by users.

Allied Health Personnel↗

Diagnostic equipment outside the laboratory.

A questionnaire was circulated to clinical biochemistry laboratories in the North West Thames region of the United Kingdom requesting information on extralaboratory equipment. Data on the types and numbers of instruments in use, their relationship with the laboratory, and quality assurance procedures were obtained. Laboratories were prepared to maintain equipment over which they had no responsibility for purchase, training of users, or use. The quality assurance of these instruments gave even greater cause for concern. Although internal quality control procedures were performed on many of the instruments, laboratories were involved in only a minority of these procedures. Quality control procedures and training of users were undertaken on site in less than 50% of blood gas analysers and bilirubin meters and in less than 25% of glucose meters. External quality assessment procedures were non-existent for all of the instruments in use with the exception of glucose stick meters in two laboratories.

Bilirubin↗

7B2, a new protein secreted by human functionless pituitary tumours, in vitro.

A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23-39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 +/- 149 pmol/l, significantly higher than that of the somatotropic tumours (248 +/- 90 pmol/l, P less than 0.05), prolactinomas (108 +/- 37 pmol/l, P less than 0.001) and corticotropin producing adenomas (107 +/- 77 pmol/l, P less than 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.

Adenoma↗

Failure to suppress GH secretion after 2 weeks treatment with atropine or propanthelene in diabetics with proliferative retinopathy.

Complete suppression of GH secretion may halt the development of retinal new vessels in patients with diabetic proliferative retinopathy. We have investigated the effectiveness of two cholinergic antagonists, atropine and propanthelene given orally for 2 weeks, in suppressing 24-h GH and IGF-I levels. Seven insulin-dependent diabetics (3 males, 4 females; aged 22-34 years) with active proliferative retinopathy and 6 matched non-diabetic normal subjects were studied in random order with at least 2 weeks between treatments. Suppression of GHRH-induced GH release was demonstrated in both groups of subjects. Twenty-four hour GH secretion was not, however, suppressed in either the patient group (mean area under the GH curve mU.l-1.h-1 +/- SD; baseline: 251 +/- 108.7; after atropine: 174 +/- 106.9; after propanthelene: 180 +/- 72.4; P greater than 0.05) or in the control group (baseline: 103 +/- 53.1; after atropine: 73 +/- 83.6; after propanthelene: 122 +/- 71.6; P greater than 0.05). GH release at times of hypoglycemia was not suppressed. Mean IGF-I concentration was not significantly reduced. Two subjects (one patient and one control) could not tolerate atropine for more than one week. We conclude that repeated doses of atropine and propanthelene do not achieve complete 24-h GH suppression and are associated with a high incidence of unpleasant adverse reactions.

Adult↗

Galanin abolishes the inhibitory effect of cholinergic blockade on growth hormone-releasing hormone-induced secretion of growth hormone in man.

In five healthy normal male volunteers, pretreatment with the cholinergic muscarinic antagonist pirenzepine (30 mg i.v.) almost abolished the growth hormone (GH) response to a maximal dose (120 micrograms i.v.) of growth hormone-releasing hormone (GHRH) (GH response at 40 min 5.6 + 1.3 mU/l with GHRH and pirenzepine vs 40.8 +/- 5.3 mU/l with GHRH alone, P less than 0.02). Concomitant i.v. infusion of galanin (40 pmol/kg/min) with pirenzepine not only restored but significantly potentiated the GH response to GHRH (GH at 40 min 72.2 +/- 10.5 mU/l, P less than 0.001 vs GHRH and pirenzepine, P less than 0.02 vs GHRH alone). Previous studies have proposed that cholinergic pathways control GH release via somatostatin and this study suggests that galanin may act by modulating hypothalamic somatostatinergic tone either directly or, possibly, by facilitating cholinergic neurotransmission.

Adult↗

Increased hypothalamic neuropeptide Y concentrations in diabetic rat.

Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) and matched control rats between 1 day and 14 wk after diabetes induction. After 2 wk, both central and lateral hypothalamic neuropeptide Y (NPY) concentrations in STZ-D rats were consistently higher than those found in control rats, with significant 30-50% increases at 4 wk in the central hypothalamus, and at 6 and 14 wk in both central and lateral hypothalamus. Immunocytochemical studies in 4- and 6-wk STZ-D animals showed the appearance of intensely NPY-positive swollen cell bodies in the supraoptic nucleus and a subjective increase in NPY staining of medial hypothalamic nerve fibers. Central hypothalamic concentrations of three other peptides were significantly greater in STZ-D animals than those in control animals at single points (neurotensin, 1 day; calcitonin gene-related peptide, 2 wk; neurokinin, 4 wk). Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time. However, galanin immunostaining in the supraoptic and magnocellular paraventricular nuclei was strikingly concentrated in a reduced number of distended cell bodies. Hypothalamic peptide changes in STZ-D could be related to metabolic disturbance, changes in energy and water balance, altered pituitary function, or other factors. Persistently elevated concentrations of NPY, a very potent central stimulant of eating and drinking, may mediate the hyperphagia and polydipsia characteristic of STZ-D.

Animals↗

Aspects of measurement and analysis of regulatory peptides.

Although almost all methods of mass measurement of regulatory peptides still depend on the high affinity antibody, the traditional Yalow and Berson radioimmunoassay technique is becoming outdated. Pure monoclonal antibodies allow excess antibody two site assay techniques with a variety of different labels (preferentially non-radioactive) of great sensitivity and speed. The large amounts of particular monoclonal antibodies available allow several different laboratories to use the same reagents and have increased comparability. Unfortunately many regulatory peptides exist in multiple molecular forms and attention must be paid to antibody region specificity. Improved methods of extraction of regulatory peptides from plasma tissue allow more accurate quantitation. New techniques for rapid high resolution chromatography make distinction of different molecular forms much easier than hitherto. Better education in techniques and/or attention to inter-assay standards are necessary to improve the comparability of regulatory peptide measurement in the future.

Animals↗

Direct assay for testosterone in saliva: relationship with a direct serum free testosterone assay.

A direct non-extraction radioimmunoassay for salivary testosterone is described using a modified commercial kit procedure that is in use for total serum testosterone (T). Serum free testosterone was also measured by direct radioimmunoassay. A significant correlation (r = 0.83, p less than 0.01, n = 194) was obtained between salivary and serum free testosterone in matched serum and saliva samples over a wide range of concentrations. Within- and between-batch precision for the salivary testosterone method was 11% and 18%, respectively at a concentration of 170 pmol/l. Recovery of added T was 89% +/- 15% (mean +/- 2 SD) dilution of high samples showed parallelism. Salivary testosterone measured by direct radioimmunoassay offers a simple cheaper alternative to serum free testosterone measurement with the additional advantages of a stress-free non-invasive sampling procedure.

Adult↗

Changes in plasma growth hormone in diabetic and nondiabetic subjects during the glucose clamp.

A group of 22 newly diagnosed noninsulin-dependent diabetic subjects and seven nondiabetic subjects underwent a glucose clamp at plasma glucose 100 mg/dL with insulin infusion rates of 1.0 and 10 mU/kg/min. During both insulin infusion rates, there was a sustained rise in plasma growth hormone (GH) above basal in 18 of the 22 diabetic subjects. Basal GH values were 2.37 +/- 0.67 ng/mL, rising above basal during the lower insulin infusion (6.1 +/- 3.3 ng/mL, P = 0.05) with a further rise at the higher insulin level (8.58 +/- 2.0 ng/mL, P less than 0.001). There was no rise in GH in any of the nondiabetic subjects. In neither group was there any rise above basal in cortisol, prolactin, glucagon, or somatostatin (SRIH). In a group of three nondiabetic subjects, a rise in GH similar to that seen in the diabetic group was induced by elevating the plasma glucose to 200 mg/dL for 60 minutes prior to the euglycemic clamp procedure. However, it is unlikely that changes in plasma glucose account totally for the changes in plasma GH described in the diabetic subjects since a rise in plasma GH was also seen in four diabetic subjects clamped at their fasting plasma glucose. We conclude that in newly diagnosed noninsulin-dependent diabetic subjects there is a rise in plasma GH during the euglycemic clamp procedure, which may be due to both the prior lowering of plasma glucose and the high plasma insulin levels.

Adult↗

Fentanyl and the beta-endorphin, ACTH and glucoregulatory hormonal response to surgery.

The effect of the supplementation of nitrous oxide-oxygen anaesthesia with either fentanyl 15 micrograms kg-1 or 0.5% halothane on the beta-endorphin, ACTH, glucoregulatory hormonal and metabolic response to pelvic surgery was investigated. Fentanyl inhibited the increases in circulating beta-endorphin, ACTH, growth hormone, cortisol and glucose concentrations found in the patients receiving halothane. Changes in circulating beta-endorphin concentrations during surgery probably reflect alterations in pituitary secretion and appear to have no major metabolic effects. The suppression of pituitary secretion persisted for at least 4 h after the start of surgery.

Adult↗

The effect of a long-acting somatostatin analogue (SMS 201-995) on intermediary metabolism and gut hormones after a test meal in normal subjects.

SMS 201-995 is an octapeptide analogue of somatostatin. The effect of a single subcutaneous (s.c.) injection of 50 micrograms SMS 201-995 on post-prandial intermediary metabolism was investigated in normal subjects. In spite of a long-lasting post-prandial suppression of insulin secretion, there were no significant changes in the plasma concentration of alanine, glycerol, 3-OH-butyrate or lactate. However, SMS 201-995 impairs carbohydrate tolerance, probably due to inhibition of insulin secretion. Basal and post-prandial plasma concentrations of the gut regulatory peptides pancreatic glucagon, motilin, pancreatic polypeptide, gastric inhibitory polypeptide, enteroglucagon, gastrin and peptide YY were suppressed up to 5 hours after subcutaneous administration of a single dose of SMS 201-995.

3-Hydroxybutyric Acid↗

Beta-endorphin infusion fails to modulate the hormonal and metabolic response to surgery.

The effects of an i.v. infusion of synthetic human beta-endorphin on the hormonal, metabolic and cardiovascular responses to surgery were investigated in female patients undergoing pelvic surgery. A beta-endorphin infusion (2 micrograms/kg as a bolus at induction of anaesthesia + 10 micrograms/kg/h for the first hour of surgery) increased plasma beta-endorphin immunoreactivity to values at least 100-fold greater than those seen during surgery in a control group of patients. In spite of this massive increase the only significant findings were a transient augmentation of the expected hyperglycaemic response and increased plasma glucagon values. There were no significant changes in ACTH, GH, insulin and cortisol secretion, in blood concentrations of lactate or glycerol, or in cardiovascular variables. Complete dissociation between plasma and cerebrospinal fluid concentrations of beta-endorphin was found even when plasma values exceeded 10,000 pmol/l in the presence of anaesthesia and surgery. These results show that the increase in circulating beta-endorphin immunoreactivity associated with clinical stress states are unlikely to modulate the associated hormonal, metabolic and cardiovascular changes.

Adult↗

Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995).

Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201-995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly.

Acromegaly↗

Hormonal and metabolic responses to cardiac surgery with sufentanil-oxygen anaesthesia.

The effects of sufentanil, 10 and 20 micrograms kg-1 on the hormonal and metabolic responses to coronary artery surgery were compared in 20 patients. The most important finding was that the changes in circulating beta-endorphin, ACTH, cortisol, GH, glucose, lactate and glycerol concentrations during and after cardiac surgery were similar with both doses of sufentanil. Although sufentanil prevented a significant increase in plasma beta-endorphin, ACTH and cortisol values until 6 h after cardiopulmonary bypass (CPB), a significant increase in GH secretion occurred with the onset of CPB. Plasma insulin concentrations declined significantly after 30 min CPB, but recovered after 60 min CPB with the restoration of normothermia. Blood glucose values did not change during surgery before CPB, but started to rise with the onset of CPB and continued to increase significantly in the postoperative period. Changes in blood lactate and plasma glycerol concentrations primarily reflected the load of CPB and the effects of heparin, respectively. The results show that increasing the dose of sufentanil up to 20 micrograms kg-1 does not result in better suppression of the endocrine and metabolic changes associated with cardiac surgery.

Adrenocorticotropic Hormone↗

The effects of cortisol supplementation on the metabolic and hormonal response to surgery.

The role of cortisol in determining the metabolic and hormonal changes associated with a standardized surgical operation was investigated. Twelve patients undergoing pelvic surgery were studied. Six received steroid supplementation with an infusion of hydrocortisone sodium succinate at a rate of 8 mg/h for 24 h, together with 1.5 g hydrocortisone acetate intraperitoneally at the completion of surgery, while the remainder acted as a control group. Steroid supplementation resulted in plasma cortisol values in the range 1913-2265 nmol/l from 4 to 24 h after the start of surgery. However, this marked hypercortisolaemia had no significant effects on circulating metabolites other than glucose, and did not alter plasma ACTH, GH and insulin values. The usual glycaemic response to surgery was significantly augmented by 1.0-1.5 mmol/l in the cortisol group. We conclude that changes in substrate mobilization observed after cortisol administration in normal volunteers may not accurately predict the effects found after surgery, when catabolic hormones and other modulators such as interleukin-1 may influence metabolism.

Adrenocorticotropic Hormone↗