Biomedical subjects

J M Burrin

Publications and source records attributed to J M Burrin.

At least 73 records · Page 4Linked to original sources

PubMed1990

Hormonal responses to cardiac surgery: effects of sufentanil, somatostatin and ganglion block.

We have investigated the effect of the addition of somatostatin and trimetaphan to sufentanil 20 micrograms kg-1 on the hormonal responses to cardiac surgery and compared the changes with a control group receiving sufentanil and sodium nitroprusside. Eighteen patients undergoing elective valve replacement surgery were studied. Patients who received somatostatin and trimetaphan in addition to sufentanil had significantly smaller serum growth hormone and plasma glucagon concentrations compared with those who received sufentanil and sodium nitroprusside. The cortisol response to surgery was inhibited in both groups. There were no significant differences in catecholamine concentrations between the two groups. There was no effect of the additional inhibition of glucagon and growth hormone on circulating concentrations of glucose and lactate, but plasma concentrations of non-esterified fatty acids increased significantly. Thus the addition of somatostatin increased the suppression of the hormonal response to cardiac surgery by sufentanil.

Aged↗

PubMed1990

Site of action of fentanyl in inhibiting the pituitary-adrenal response to surgery in man.

To determine the site of action of fentanyl in attenuating the pituitary-adrenal response to surgery, we have measured serum concentrations of cortisol and growth hormone during and after a standardized surgical procedure in two groups of patients. One group received fentanyl 15 micrograms kg-1 i.v. immediately before the start of surgery; a second group received fentanyl 15 micrograms kg-1 i.v. together with corticotrophin releasing factor 100 micrograms i.v., growth hormone releasing hormone 100 micrograms i.v. and arginine vasopressin 10 units i.m. The concomitant administration of the releasing factors with the opioid resulted in a significantly greater serum concentration of cortisol 30, 60, 120 and 240 min after surgery commenced, compared with the group which received fentanyl alone. Similarly, the growth hormone response in the combined group was significantly greater than in the fentanyl-alone group 30 min after the start of surgery. We conclude that the inhibitory effect of fentanyl on surgically-induced secretion of pituitary hormone was mediated directly or indirectly via the hypothalamus.

Arginine Vasopressin↗

PubMed1990

An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings.

The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m. or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l. In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m. serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH. A mean suppressed value of greater than 450 nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH.

ACTH Syndrome, Ectopic↗

PubMed1990

The influence of thyroid hormone status on the hypothalamo-hypophyseal growth hormone axis.

Growth hormone (GH) synthesis is known to be impaired by either abnormally high or low levels of thyroid hormone. To determine the effects of these conditions on the central regulation of GH secretion, we have examined their effects on the hypothalamic regulatory peptides GH-releasing hormone (GH-RH) and somatostatin (SRIF). In thyroidectomized rat hypothalamus, a dramatic increase in GH-RH mRNA occurred in parallel with a decrease in peptide content. The significance of this phenomenon is uncertain and might possibly reflect some posttranscriptional derangement of GH-RH synthesis or an increased rate of GH-RH synthesis and release. In the hyperthyroid group, GH-RH showed significant decreases in both peptide and mRNA levels that might possibly reflect a decrease in GH-RH synthesis and secretion. No change was observed in SRIF peptide or mRNA levels in either thyroidectomized or T4-treated animals. As expected, GH mRNA levels in the anterior pituitary were dramatically decreased by thyroidectomy and unaffected by T4 treatment. In addition, in thyroidectomized pituitaries, the mature GH mRNA was observed to alter its structure, increasing in size by approximately 100 nucleotides. This increase in size was found to result from an increase in poly(A) tail length, the significance of which is as yet unclear.

Animals↗

PubMed1990

Divergent responses of gonadotropin subunit messenger RNAs to continuous versus pulsatile gonadotropin-releasing hormone in vitro.

Episodic GnRH input is necessary for the maintenance of LH and FSH secretion. In the current study we have assessed the requirement of a pulsatile GnRH signal for the regulation of gonadotropin alpha- and beta-subunit gene expression. Using a dispersed rat pituitary perifusion system, GnRH (10 nM) was administered as a continuous infusion vs. hourly pulses. Secretion of free alpha-subunit, LH, and FSH were monitored over 5-min intervals for the entire 12-h treatment period before the responses of alpha, LH beta, and FSH beta mRNAs were assessed. Basal release of all three glycoproteins declined slowly over 6-8 h before reaching a plateau. The cells were responsive to each pulse of GnRH, but continuous GnRH elicited only a brief episode of free alpha-subunit, LH, and FSH release, followed by a return to unstimulated levels. Despite the similar patterns of secretion, differences were observed in the responses of gonadotropin mRNAs to the two modes of GnRH. alpha mRNA increased in response to continuous (1.6-fold) or pulsatile (1.7-fold) GnRH. FSH beta mRNA was suppressed to 48% of the control value after continuous GnRH, but was stimulated over 4-fold by the pulses. LH beta mRNA was unresponsive to either treatment paradigm. We conclude that in vitro 1) alpha mRNA levels are increased in response to GnRH independent of the mode of stimulation; 2) under the conditions studied, LH beta mRNA levels are unresponsive to either mode of GnRH input; and 3) the response of FSH beta mRNA to GnRH is highly dependent on the mode of administration, with levels depressed in response to continuous GnRH, but stimulated by pulsatile GnRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Serum testosterone levels in women with Cushing's disease.

Serum testosterone was measured pre- and post-operatively in 31 women who obtained remission of Cushing's disease following treatment by interstitial irradiation of the pituitary gland. The mean serum testosterone was initially elevated at 3.35 nmol/l, with values ranging from 0.7 to 14.4 nmol/l. Following treatment the mean serum testosterone fell to 1.42 nmol/l (i.e. normal) and all but one of the 15 patients with initially elevated pre-treatment values obtained normal levels. The pretreatment testosterone concentrations correlated significantly (r = 0.47; p = 0.019) with the midnight ACTH concentration. The likely determinant of the raised serum testosterone would appear to be the intensity of the ACTH drive, although an individual's inherent sensitivity to ACTH may also be a factor.

Adolescent↗

PubMed1990

Effects of a novel 21-amino steroid, U74006F, on the rat pituitary-adrenocortical axis.

The 21-amino steroid U74006F is a potent inhibitor of lipid peroxidation and has been shown to affect beneficially the acutely injured central nervous system. Therapeutically, it is desirable for this compound to be devoid of steroid side-effects. We have demonstrated a significant (P less than 0.001) inhibition of basal ACTH secretion from cultured rat pituitary cells during a 24-h incubation at concentrations (10-100 mumols/l) previously demonstrated to inhibit lipid peroxidation in vitro. U74006F also inhibited corticotrophin-releasing factor (CRF)-stimulated ACTH secretion significantly and the combination of dexamethasone and U74006F completely blocked CRF-41-stimulated ACTH secretion. Administration of U74006F in vivo (30 mg/kg, orally, every 6 h for 30 h) had no effect on ACTH levels in normal rats (84 +/- 38 vs 45 +/- 6 ng/l in control animals) but increased ACTH levels in adrenalectomized rats (1330 +/- 295 vs 464 +/- 79 ng/l in control animals, P less than 0.02). This increase in ACTH was not observed when adrenalectomized animals were maintained on the same regime of U74006F for 5 days. Our data suggest that U74006F is capable of exerting inhibitory effects on ACTH secretion in vitro. In vivo, effects on ACTH secretion were stimulatory rather than inhibitory and only occurred short-term in adrenalectomized animals or chronically in adrenalectomized rats maintained on dexamethasone. No effects on the pituitary-adrenocortical axis were seen following short-term or chronic administration of U74006F in normal rats.

Adrenalectomy↗

PubMed1990

Flow cytometric analysis of functional anterior pituitary cells from female rats.

Laser-light scatter signals generated from living cells provide useful information with regard to both cell size (forward-angle light scatter) and granularity (ninety-degree or perpendicular light scatter). By measuring angles of light scatter and fluorescence, a fluorescence-activated cell sorter is capable of analysing and sorting cells on the basis of their size, granularity and cell-surface fluorescence. Using an electronically programmable individual cell sorter we were able to analyse single, viable, dispersed anterior pituitary cells of the female rat on the basis of their laser light scatter characteristics. Two distinct populations of differing granularity were defined: 26 +/- 2.2% (mean +/- S.E.M.) were more granular and 74 +/- 3.5% less granular. Acutely dispersed anterior pituitary cells were labelled with antibodies against four of the anterior pituitary hormones, and cell size and granularity were compared amongst the different hormonal cell types. Somatotrophs were the most granular cell type, gonadotrophs were the largest and corticotrophs the smallest, whilst lactotrophs were of intermediate size. Labelling was demonstrated to be dependent upon the secretory state of the cell. Hypothalamic stimulating factors increased cell-surface labelling, whilst dopamine and somatostatin decreased labelling. These changes compare favourably with published data obtained by immunocytochemistry. Using dual-colour fluorescence cell surface labelling we were unable to define a population of cells secreting both prolactin and growth hormone (mammosomatotrophs).

Adrenocorticotropic Hormone↗

PubMed1990

Purification of functional lactotrophs and somatotrophs from female rats using fluorescence-activated cell sorting.

As the secretory granules of anterior pituitary cells fuse with the cell surface, there would appear to be sufficient hormone present on the cell surface to be labelled by polyclonal hormone antibodies and thus analysed by flow cytometry. We have therefore applied fluorescence-activated cell sorting to these labelled pituitary cells. Percentage purity and depletion of other cell types was assessed by immunocytochemistry and the reverse haemolytic plaque assay (RHPA). Results demonstrate that fluorescence-activated cell sorting allows almost complete purification of functional lactotrophs and somatotrophs to 96.7 +/- 1.7 (S.E.M.)% and 98 +/- 1.0% respectively by immunocytochemistry, and to 95.8 +/- 1.1% and 97 +/- 0.8% respectively by RHPA. Depletion of other anterior pituitary cell types to less than 2% was demonstrated by both immunocytochemistry and RHPA. Fluorescence-activated cell sorting to this degree of purity was routinely possible with cell yields of 91 +/- 3.4%. To obtain such purity/depletion, it was necessary to use specific antisera of high titre, at concentrations which ensured maximal cell-surface labelling associated with maximal stimulation of hormonal secretion by the appropriate hypothalamic stimulatory factor. Separating cells on the basis of the intensity of prolactin cell-surface labelling demonstrated a low level of binding of the prolactin antibody to gonadotrophs (but not of sufficient fluorescence intensity to be sorted into the prolactin enriched population), raising the possibility of prolactin receptors on gonadotrophs. We were unable to demonstrate the presence of mammosomatotrophs in the normal female rat, since purified lactotrophs did not contain or secrete GH nor did purified somatotrophs contain or secrete prolactin.

Animals↗

PubMed1990

Intracellular mechanisms involved in the stimulation of growth hormone release from rat anterior pituitary cells by Russell's viper venom.

We have previously shown that a heat-stable component of Russell's viper venom (RVV) releases GH in a dose-dependent manner from cultured rat anterior pituitary cells. We have now investigated the intracellular mechanisms involved in RVV-stimulated GH release by concomitant administration of RVV with known intracellular mediators in rat pituitary cells. 3-Isobutyl-1-methylxanthine (IBMX; 0.5 mmol/l), added to cultured rat anterior pituitary cells simultaneously with RVV, at concentrations up to a maximally effective dose of 10 micrograms/ml, increased GH release (3.7-fold, 4.0-fold and 2.0-fold; P less than 0.001) compared with the effect of venom alone. These effects were additive, indicating that RVV and IBMX stimulate through different intracellular messengers. RVV failed to increase the formation of basal or IBMX-stimulated intracellular cyclic AMP (cAMP), confirming that RVV affects GH release through a cAMP-independent pathway. 12-0-Tetradecanoylphorbol-13-acetate (TPA; 0.1 mumol/l), added simultaneously with various doses of RVV (0.1-10 micrograms/ml), did not increase GH release beyond the maximal effect of RVV. This result indicates that RVV might be stimulating GH release through a similar mechanism to that of TPA (by activating protein kinase C). When pituitary cells were perifused with Ca(2+)-free medium or verapamil (50 mumol/l), RVV-stimulated GH release was inhibited by 65 and 42% respectively. This reflects the recognized requirement of Ca2+ for secretory processes. However, RVV (10 micrograms/ml) had no significant effect on intracellular free Ca2+ concentrations as measured using the fluorescent Ca2+ probe quin-2.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1990

Immediate and long-term effects on hormone levels following bites by the Burmese Russell's viper.

Studies of anterior pituitary function were made in victims of a bite by the Burmese Russell's viper, who had required admission to a renal unit. Twenty patients at the stage of the acute illness were studied using a single blood sample for several hormone assays. None showed normal levels of all hormones measured. As acute severe illness can have a profound effect on the levels of these hormones, it is only possible to conclude that the results were compatible with although not diagnostic of anterior pituitary failure. Twelve survivors were assessed at eight to 226 weeks after envenoming, by hormone measurement in a basal sample, and a combined pituitary reserve function test with TRH, GnRH, and insulin hypoglycaemia. All but one showed some deficit in pituitary hormone secretion. Seven had already been started on thyroid replacement therapy or corticosteroids. Three survivors were assessed in the acute stage and later and each had similar findings on both occasions. Three survivors who were followed up and assessed with a combined pituitary reserve function test on two occasions had similar results each time. There was no sign of recovery. It seems that severe envenoming may be associated with anterior pituitary failure. Results from five autopsies showed that the lesion was haemorrhagic anterior pituitary necrosis. An additional mechanism may be direct action of the venom upon the function of anterior pituitary cells. We conclude that severely affected victims should be considered at risk of pituitary insufficiency.

Acute Disease↗

PubMed1989

A two-year follow-up study of serum insulinlike growth factor-I in diabetics with retinopathy.

Serum insulinlike growth factor-I (IGF-I) concentration was evaluated prospectively over two years in 35 diabetic patients with severe background or preproliferative retinopathy (group 1) and 24 diabetics with mild background retinopathy matched for age, sex, and glycemic control (group 2). In addition, 12 normal subjects were also studied to assess the variability of individual serum IGF-I levels over two years. Mean serum IGF-I (+/- SD) micrograms/l at entry, one year, and two years was not significantly different in the patient groups (157 +/- 71 v 168 +/- 77; 166 +/- 78 v 159 +/- 87; 143 +/- 58 v 159 +/- 67) or when compared with the normal subjects (181 +/- 47, 188 +/- 30; 221 +/- 56). Eight patients in the preproliferative group and none in the mild background group developed proliferative retinopathy. In this subgroup developing retinal neovascularization, serum IGF-I at the time of the first appearance of retinal new vessels was significantly higher than 3 months (1 to 4 months) before the onset of proliferation (271 +/- 94 v 196 +/- 58; P = .036). Values at the time of proliferation were not, however, significantly different from the mean serum IGF-I value of all patients in group 1 and by 4 months (3 to 6 m) had returned to their previous values. Although a transient elevation of IGF-I occurs at the time of retinal new vessel formation, the rise in serum concentration is not sufficiently great or early enough to be of clinical value as a predictor of retinal neovascularization.

Adult↗

PubMed1989

Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII).

The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine.

We have studied the metabolic and hormonal responses to surgery, and the pain scores and analgesic requirements in 24 patients undergoing cholecystectomy, allocated randomly to three groups to receive either general anaesthesia alone, or general anaesthesia with extradural diamorphine 0.1 mg kg-1, or general anaesthesia with extradural somatostatin to a total dose of somatostatin 3 mg. The only significant effect of extradural diamorphine was a decrease in the glucose response to surgery. Somatostatin 3 mg by the extradural route caused a significant increase in the concentration of circulating somatostatin which resulted in a significant decrease in plasma growth hormone and insulin after 60 min of surgery, together with an increase in plasma glycerol concentration. Patients in the diamorphine group required significantly less i.v. analgesia in the postoperative period than the other two groups. Intraoperative somatostatin failed to provide any postoperative analgesia.

Adult↗

PubMed1989

Effects of epidural analgesia on plasma calcitonin gene-related peptide.

The effects of epidural analgesia on plasma calcitonin gene-related peptide (CGRP) values during and after hysterectomy were investigated in 14 healthy patients. In seven patients who received general anaesthesia alone for pelvic surgery, there were no significant changes in plasma CGRP concentrations. In the remaining patients, who received extensive epidural blockade in addition to general anaesthesia, there were again no significant changes in plasma CGRP values. This was in spite of profound sympathetic blockade, as shown by marked hypotension and a significant decline in plasma catecholamines. The epidural group of patients showed the expected attenuation of the glucose, cortisol and growth hormone responses to surgery. The results show that circulating CGRP is unlikely to be involved in the modulation of peripheral vascular tone during pelvic surgery under either general or epidural anaesthesia.

Adult↗

PubMed1989

A comparison of human ultralente- and lente-based twice-daily injection regimens.

The problem of fasting hyperglycaemia remains unresolved on currently used twice-daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc-insulin complex. In a 6-month double-blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice-daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 +/- 0.5 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 +/- 0.2%). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 +/- 0.8 vs 15.5 +/- 0.8 U, p less than 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 +/- 0.10 vs 0.09 +/- 0.04 events per patient-month, p less than 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice-daily injection regimen.

Adult↗

PubMed1989

Use of adrenal arterial embolization in severe ACTH-dependent Cushing's syndrome.

The management of a patient with severe Cushing's syndrome due to ectopic ACTH produced by a medullary carcinoma of the thyroid is described. Initial treatment with maximal adrenolytic medical therapy and two attempts at bilateral adrenal venous infarction had failed to control the disease, and she was at that time unfit for surgery. Subsequent use of bilateral adrenal arterial embolization enabled medical therapy to produce sufficient control of the Cushing's syndrome to allow bilateral adrenalectomy to be performed successfully, with resultant cure of the excessive cortisol production.

ACTH Syndrome, Ectopic↗

PubMed1989

Evidence for neuropeptide Y synthesis in the rat anterior pituitary and the influence of thyroid hormone status: comparison with vasoactive intestinal peptide, substance P, and neurotensin.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in the rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) was identified in the pituitary by Northern blot analysis. The possible regulation of NPY was examined by determining the effects of thyroid hormone manipulation on peptide synthesis. Three other anterior pituitary neuropeptides, neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP), were studied for comparison. Hypothyroidism was found to significantly increase the pituitary content of NPY, SP, and VIP and their respective mRNAs but to decrease the quantity of NT. Immunocytochemistry revealed very weak NPY immunoreactivity in scattered cells in control rat anterior pituitaries, but in hypothyroid rats a greater number of positive cells were seen, and the staining was relatively intense. These positive cells were identified as a subset of thyrotropes. In T4-induced hyperthyroidism NPY, NT, and VIP levels were unaffected whereas SP concentrations fell considerably. TRH treatment produced a decrease in NT and had no effect on NPY, SP, or VIP. These changes were found only in the pituitary; no net change occurred in hypothalamic peptide and mRNA levels. Since the changes in pituitary peptide and mRNA levels occurred coordinately it appears that regulation by thyroid hormone status occurs, at least in part, directly at the level of gene transcription. The changes in these 4 regulatory peptides in hypothyroidism and their known powerful effects on pituitary function suggest that they may have a significant paracrine or autocrine influence in controlling the alterations in pituitary secretion.

Animals↗