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J M Burrin

Publications and source records attributed to J M Burrin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Serum cytokines in thyrotoxicosis.

Overproduction of thyroid hormones promotes bone resorption in vivo and in vitro, and we have evaluated whether mediators of such effects could include the osteotropic cytokines. Previous studies have demonstrated raised serum interleukin (IL)-6 in thyrotoxic patients, but differentiating the contribution of the elevated thyroid hormones from that of the autoimmune inflammation present in Graves' disease (GD) has been difficult. We undertook a longitudinal study of 34 patients (19-45 yr old) with GD, toxic nodular goiter (TNG), or a history of thyroid carcinoma but no evidence of disease recurrence, receiving sufficient T4 to suppress TSH. Controls were 12 euthyroid females. The following measurements were made basally and for 6 months after carbimazole treatment: serum free T4, T3, bone-specific alkaline phosphatase (b-ALP), IL-6, IL-8, IL-1beta, tumor necrosis factor-alpha, IL-11, and urinary deoxypyridinoline (Udpd). Compared with controls (IL-6, 1.1 +/- 0.3 ng/L; IL-8, 3.2 +/- 0.8 ng/L), untreated patients with GD and TNG had elevated IL-6 (GD, 7.11 +/- 0.88 ng/L; TNG, 7.30 +/- 0.77 ng/L; P < 0.001) and IL-8 (GD, 10.3 +/- 1.23 ng/L; TNG, 9.81 +/- 1.27 ng/L; P < 0.001). These levels fell after treatment and were then indistinguishable from those in control subjects. Thyroid carcinoma patients on TSH suppressive therapy also had significantly raised levels of IL-6 (2.5 +/- 0.42 ng/L) and IL-8 (4.4 +/- 0.63 ng/L). When data from all the patients were pooled, the levels of IL-6 and IL-8 correlated with serum T3 and free T4 but not with Udpd or b-ALP. IL-1beta, IL-11, and tumor necrosis factor-alpha were not raised in any patient. The elevations in serum IL-6 and -8 that occur in hyperthyroidism seem to result from the chronic effects of thyroid hormone excess rather than the accompanying autoimmune inflammatory condition produced by Graves' thyroid or eye disease. The site of the presumed increased production of IL-6 and -8 is most likely from bone osteoblasts, despite the inability of bone markers (such as Udpd and b-ALP) to correlate with acute changes in thyroid hormone status produced by antithyroid therapy.

Adult↗
PubMed1999

Steroidogenic factor 1-DNA binding: a kinetic analysis using surface plasmon resonance.

Basal expression of the glycoprotein hormone alpha-subunit gene in pituitary gonadotrophs is partially dependent on a gonadotroph specific element (GSE) which binds the nuclear receptor, steroidogenic factor-1 (SF-1). We have used surface plasmon resonance (SPR) to determine the association (kappa ass), dissociation (kappa diss) and affinity (KA) constants of SF-1 binding to immobilized oligonucleotides containing either the GSE consensus motif or a GSE mutant with a 2 bp substitution in the GSE site (GSEMUT). In vitro translated SF-1 protein bound the consensus GSE with a threefold increase in affinity constant (P<0.01) compared with the GSEMUT. This was due primarily to a significant increase (P<0.05) in the kappa ass for SF-1 to the GSE and a slower kappa diss (P<0.05). The binding interaction was specific and could be significantly inhibited (P<0. 001) by either anti-SF-1 antibody or excess non-biotinylated GSE. The addition of 14 bp wild-type flanking sequences significantly reduced the affinity of SF-1 to both the GSE (P<0.05) and the GSEMUT (P<0.01). This was due to a significant (P<0.01) decrease in kappa ass for the wild-type and mutant long oligonucleotides compared with the short GSE. Nuclear extracts from alphaT3-1 gonadotroph cells also bound the GSE and GSEMUT, giving kappa diss values which were two- to threefold slower than those obtained with in vitro translated SF-1. Thus, SPR is a powerful technique for examining kinetic interaction between SF-1 and its binding site, and is able to demonstrate the effects of mutations and flanking sequences on that interaction.

Base Sequence↗
PubMed1998

The matrix effects on kinetic rate constants of antibody-antigen interactions reflect solvent viscosity.

This study describes the influence of different matrices on two model antibody-antigen interactions; that between beta2microglobulin and anti beta2microglobulin, and that of rabbit anti mouse Fc fragment (RAMFc) with mouse IgG. The matrices investigated were; phosphate-buffered saline pH 7.4 containing 0.05% Tween 20 detergent, horse serum, a 50:50 mixture of phosphate-buffered saline/Tween 20 and horse serum, and four glycerol solutions of differing concentrations. A recently developed optical biosensor, the IAsys, was used to monitor the interactions in real-time and provide precise determinations of k(ass), k(diss) and KA values. The results show that the rates of association and dissociation for the two different antibody:antigen models are significantly affected by the surrounding matrix. Glycerol of known viscosity was used as a matrix in both models to show that this effect is attributable to the viscosity as opposed to proteins present in the matrix. The viscosity of the matrix has also been shown to have an apparent influence upon the overall equilibrium/affinity constant for the interaction, with measurements of KA tending to increase with viscosity. The significant effects of matrix on kinetic rate constants for antibody-antigen interactions shown here have important implications in the use of immunoassays where non-equilibrium measurements are made in serum matrices.

Animals↗
PubMed1998

Pituitary-adrenal, hormonal changes during induced hypotension with labetol or isoflurane for middle-ear surgery.

BACKGROUND: Pituitary-adrenal secretion during induced hypotension for middle-ear surgery has received little attention. Previous work failed to differentiate the effects of induced hypotension from surgical stimulation. We have undertaken a preliminary study examining the effects of hypotension, achieved with labetalol or isoflurane, on pituitary-adrenal secretion before, during and after middle-ear surgery. METHODS: Twenty-four patients were allocated randomly to 3 groups. The control group were anaesthetised with isoflurane, and normotension maintained for 30 min before hypotension was induced with isoflurane and surgery started. In the labetalol group, this drug was given i.v. to obtain a mean arterial pressure (MAP) of 60 mm Hg for 30 min before surgery and hypotension maintained with labetalol during the operation. In the isoflurane group, hypotension was induced to a MAP of 60 mm Hg for 30 min before surgery and continued throughout the procedure. All 3 groups received metoprolol i.v. before hypotension was established. Blood samples were collected before induction of anaesthesia, during anaesthesia alone (normotensive or hypotensive), surgery with hypotension, and recovery. They were analysed for adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), cortisol and aldosterone. RESULTS: Induced hypotension before surgery failed to stimulate release of ACTH, AVP and cortisol. No significant increase in these hormones occurred until the postoperative period. Aldosterone concentrations increased significantly during anaesthesia and hypotension in the labetalol and isoflurane groups (P<0.05) and continued to rise significantly in all 3 groups during surgery. However, there was no significant difference in aldosterone concentration before surgery between the control and the 2 hypotensive groups. CONCLUSION: ACTH, AVP and cortisol secretion were not stimulated by induced hypotension to MAP of 60 mm Hg before surgery. Increased aldosterone secretion occurred and a further study with a larger sample size is needed.

Adrenal Cortex Hormones↗
PubMed1998

Mechanism of action of pituitary adenylate cyclase-activating polypeptide on human glycoprotein hormone alpha-subunit transcription in alphaT3-1 gonadotropes.

Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to increase glycoprotein hormone alpha-subunit synthesis and release from pituitary cells. We have used alphaT3-1 clonal gonadotropes to investigate the intracellular mechanisms involved in PACAP regulation of alpha-subunit gene transcription; and using deletion, mutation, and heterologous constructs of the alpha-promoter linked to a luciferase reporter gene, we have defined DNA sequences responsive to PACAP. Stimulation of alphaT3-1 cells for 24 h with PACAP, GnRH, or vasoactive intestinal peptide (VIP) resulted in a time- and concentration-dependent increase in alpha-promoter transcription at 100 nM for GnRH (17.5-fold, P < 0.001), PACAP (12.7-fold, P < 0.01), and VIP (4.1-fold, P < 0.05). Incubation of alphaT3-1 cells in calcium-depleted medium suggested that the transcriptional response to PACAP was less dependent on changes in intracellular calcium concentration, in contrast to the results seen with GnRH or VIP, where alpha-subunit transcription was significantly reduced. Transfection of an alpha-promoter construct containing a mutant cAMP response element (CRE) suggested that the CRE region is involved in PACAP and VIP responsiveness, with stimulatory effects on the mutant construct by PACAP (11.1-fold) and VIP (7.6-fold) being significantly (P < 0.001) reduced, compared with their stimulatory effects (PACAP: 25.6-fold, VIP: 23.1-fold) on the native alpha-promoter. In the same experiment, the transcriptional response of the mutant CRE construct and the native CRE construct to GnRH was not significantly different. Both PACAP and VIP enhanced GnRH-stimulated alpha-subunit gene transcription, but this additive effect was lost when their combined effects on the mutant CRE were examined. Deletion analysis indicated that sequences between -244 and -195 bp were involved in mediating the response to PACAP, with a dramatic reduction in fold-stimulation by PACAP (2.0-fold) of the -195-bp construct, compared with the -244-bp construct (15.8-fold). Constructs containing only upstream alpha-promoter sequences from -517 bp to -98 bp, fused to the heterologous thymidine kinase promoter, exhibited a similar loss of responsiveness to PACAP below -298 bp. Thus, our studies show that, unlike GnRH, PACAP stimulation of alpha-subunit gene transcription in alphaT3-1 cells is less dependent on changes in intracellular calcium concentration; and full transcriptional activation of the alpha-subunit by PACAP requires an intact CRE. PACAP responsiveness involves sequences between -244 and -195 bp of the alpha-promoter. These sequences have been implicated also in GnRH-responsiveness and may thus provide a mechanism for coordinated regulation of the alpha-subunit gene by PACAP and GnRH in alphaT3-1 cells.

Animals↗
PubMed1998

Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors.

Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide mimetics) stimulate GH release, activate the hypothalamo-pituitary-adrenal axis, and release PRL in vivo. Patients with acromegaly show an exuberant GH response to GHSs, whereas patients with pituitary-dependent ACTH-secreting tumors show an exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3 insulinomas, and a non-secreting thymic carcinoid as well as in 7 normal pituitary glands. Certain pituitary tumors were also studied by in vitro cell culture with measurement of secreted GH, ACTH, PRL, FSH, LH, alpha-subunit, and TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R expression. All the somatotroph adenomas (n = 8) showed a 2-10 times higher expression of the GHS-R gene compared to normal pituitaries. Higher than normal expression was shown in 5 of 18 tumors from patients with ACTH-secreting pituitary adenomas and in 1 of 3 ectopic ACTH-secreting carcinoid tumors. Two of the pituitary ACTH-secreting adenoma samples showed completely absent expression of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and 3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors showed a very low level of expression. One of 4 prolactinoma samples showed a high level of expression, 1 showed expression similar to that of normal pituitary, and 2 samples showed a very low level of expression. Nonfunctioning pituitary adenoma samples showed either absent or very low level expression of the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of normal pituitary tissue, whereas 3 insulinomas showed low level expression of the GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable expression. In summary, although GHS-R messenger RNA is abundant in human somatotroph adenomas, it is also present in other pituitary adenomas, particularly ACTH-secreting tumors. These findings may explain the in vivo responses to GHSs in patients harboring such tumors. It also appears from our study that GHS-R may be expressed in other neuroendocrine tumors.

Acromegaly↗
PubMed1998

Free alpha-subunit and intact TSH secretion in vitro are closely associated in human somatotroph adenomas.

OBJECTIVE: GH-secreting pituitary adenomas frequently co-secrete prolactin and glycoprotein hormone alpha-subunit (alphaSU), but expression of additional hormones is considered unusual. The aim of this study was to establish the frequency with which acromegalic tumours secrete intact glycoprotein hormones LH, FSH and TSH, in comparison with other types of pituitary adenoma. DESIGN AND METHODS: Pituitary tumours were studied by cell culture, measuring the basal secretion of anterior pituitary hormones in vitro. Light microscopy was used to exclude tumours where normal pituitary tissue was present, and immunocytochemistry was employed to confirm the clinical diagnosis and for comparison with tissue culture data. RESULTS: TSH secretion was observed in vitro in 15/23 somatotroph adenomas, but from only 1/8 lactotroph, 4/29 null cell, 2/12 gonadotroph and 1/10 corticotroph adenomas; moreover, somatotroph adenomas secreted the largest amounts of TSH (P < 0.(001). Somatotroph adenomas also secreted LH (7/23) and FSH (2/23) but less frequently than gonadotroph adenomas. Immunocytochemistry demonstrated glycoprotein expression in somatotroph adenomas (LHbeta: 13%, FSHbeta: 26%, TSHbeta: 30%, alphaSU: 46%) more frequently than in lactotroph, corticotroph and null cell adenomas. A strong correlation was found between alphaSU secretion and TSH secretion in somatotroph adenomas (rho= 0.683, P < 0.001. CONCLUSIONS: TSHbeta is frequently expressed by somatotroph adenomas, often associated with alphaSU expression. Both GH and TSHbeta are dependent on the transcription factor, Pit-1, which is frequently expressed in somatotroph adenomas, although the expression of alphaSU requires an alternative explanation. Increased expression of alphaSU compared with TSHbeta may account for the secretion of free alphaSU by somatotroph adenomas.

Adenoma↗
PubMed1998

Tri-iodothyronine regulates the production of interleukin-6 and interleukin-8 in human bone marrow stromal and osteoblast-like cells.

Hyperthyroidism is associated with increased bone resorption but the mechanisms by which thyroid hormone (T3) affects bone cell metabolism remain unclear. Recently it has been suggested that T3 stimulates osteoclastic resorption indirectly through the release of soluble mediators from osteoblasts. The aim of the present study was to investigate whether the T3-induced increase in bone resorption could be due to the regulation of cytokine production by human osteoblasts (hOb). The effects of T3 (1, 10, 100 nM) and IL-1 beta (100 U/ml) as the positive control were examined on cytokine protein release and mRNA levels in cultured hOb cell lines (MG63, SaOs-2), primary hOb and human bone marrow stromal (hBMS) cells. T3 increased IL-6 and IL-8 mRNA levels as well as IL-6 and IL-8 protein release into the culture media from MG63 and hBMS cells in a time- and dose-dependent manner. The maximal effect on protein release in hBMS cells occurred at 24 h with a dose of T3 10 nM (IL-6 5.5 +/- 1.1-fold above controls; IL-8 3.7 +/- 0.5-fold above controls, P < 0.05). At the same time, mRNA levels in hBMS cells were increased 6.2 +/- 0.8-fold for IL-6 (P < 0.05) and 5.7 +/- 0.8-fold for IL-8 (P < 0.05). Similar results were obtained in MG63 cells but no response was seen in SaOs-2 or hOb cells despite measurable basal production. Nor was there detectable regulation of IL-1 beta, IL-3, IL-11, IL-4 or granulocyte macrophage-colony stimulating factor by T3 in any cell type. In conclusion, T3 increases IL-6 and IL-8 production by MG63 and hBMS cells, suggesting that IL-6 and IL-8 may be T3-regulated genes in osteoblasts.

Bone Marrow Cells↗
PubMed1997

Lessons for the laboratory from a general practitioner survey.

AIMS: To assess the current performance of the clinical biochemistry service provided to general practitioners, with particular attention to result turnround times, and to identify and improvements required. METHODS: Postal questionnaire survey of general practitioners in the London Borough of Tower Hamlets who used the clinical biochemistry laboratory of the Royal London Hospital. A flow analysis study of turnround times for general practitioner samples was also performed. RESULTS: Responses to the questionnaire showed that although 82% of general practitioners thought the current quality of service provided was better than fair, the actual turnround times achieved were longer than the acceptable times required. There was also a strong demand (> 66% of responders) for additional information-such as highlighting of abnormal results-to be provided with results. There was wide variability between practitioners in their use of the laboratory (from none to > 800 requests per year), with no apparent correlation to practice size. Of the repertoire of tests requested, a surprisingly high percentage (14.3%) were for thyroid function. Flow analysis of turnround times for thyroid function tests showed that problems lay not with the time taken for analysis (only 7.8% of the total turnround time) but with the pre- and postanalytical phases, that is, the sample collection and results delivery service. CONCLUSIONS: Increasing the proportion of health care delivered in the primary care sector will inevitably increase the requirement for pathology services. Improvements in the specimen collection and results delivery service to general practitioners are needed to meet their expectations. It remains to be determined whether increased investment in these aspects of laboratory service would result in improved patient care in the primary sector.

Biochemical Phenomena↗
PubMed1997

A longitudinal study of markers of bone turnover in Graves' disease and their value in predicting bone mineral density.

Whether biochemical markers can predict improvement in reduced bone mineral density (BMD) associated with thyrotoxicosis in unclear. We investigated the relationship between serum osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP), serum deoxypyridinoline (Sdpd) and pyridinoline (Spyr), 24-hour urinary deoxypyridinoline (Udpd), and BMD in 17 thyrotoxic patients during 1 yr of treatment. Coinciding with euthyroidism at 4-8 weeks, there was a peak in b-ALP and OC and a prompt fall into the normal range in Udpd and Sdpd, but not Spyr, levels. Mean b-ALP continued to be raised at week 52 when it was inversely correlated with BMD. Mean BMD rose approximately 6%, P < 0.01, over 1 yr. Coupling indices were calculated as a measure of bone balance and, at diagnosis, was [minus4.26 in favor of bone resorption and rose with treatment in favor of bone formation: weeks 2: -0.23; 4: +4.01; 8: +4.37; 12: +4.44; 24: +2.32; and 52: +1.56. Bone turnover is balanced within 2 weeks of starting treatment for thyrotoxicosis. Udpd accurately indicates thyrotoxic bone resorption. Serum b-ALP indicates continuing bone formation and, at 1 yr, may provide a marker for low BMD. OC, Sdpd, and Spyr are less sensitive in documenting bone remodeling during treatment of thyrotoxicosis.

Adult↗
PubMed1996

Growth hormone responses to treadmill sprinting in sprint- and endurance-trained athletes.

The purpose of the present study was to examine the growth hormone (GH) response to treadmill sprinting in male (M) and female (F) sprint- and endurance-trained athletes. A group of 11 sprint-trained (ST; 6M, 5F) and 12 endurance-trained (ET; 6M, 6F) athletes performed a maximal 30-s sprint on a nonmotorized treadmill. Peak power and mean power expressed in watts or in watts per kilogram body mass were higher in ST than in ET (P < 0.01) and in the men compared to the women (P < 0.01). Serum GH was greater in ST than in ET athletes, but was not statistically significantly different between the men and the women [mean peak GH: ST 72.4 (SEM 12.5) compared to ET 26.3 (SEM 4.9) mU.1(-1), P < 0.01; men 59.8 (SEM 13.3) compared to the women 35.8 (SEM 7.4) mU.1(-1), n.s.]. Plasma ammonia and blood lactate concentrations were higher and blood pH lower during 1 h of recovery after the sprint in ST compared to ET (all P < 0.01). Multiple log linear regression showed that 82% of the variation in the serum peak GH response was explained by the peak power output and peak blood lactate response to the sprint. As serum GH was still approximately ten times the basal value in ST athletes after 1 h of recovery, it is suggested that the exercise-induced increase in GH could have important physiological effects in this group of athletes, including increased protein synthesis and sparing of protein degradation leading to maintained or increased muscle mass.

Adult↗
PubMed1996

Calcium and glycoprotein hormone alpha-subunit gene expression and secretion in alpha T3-1 gonadotropes.

GnRH stimulates both transcription and secretion of the alpha-subunit in pituitary cells, but the precise role of the calcium- signaling mechanisms mediating these actions are unclear. We have examined the role of calcium using alpha T3-1 gonadotropes transfected with alpha-promoter constructs linked to a luciferase reporter gene and concomitant measurement of alpha-subunit secretion. The calcium channel agonist, BayK8644 (1 microM) significantly stimulated alpha-subunit transcription (4.9-fold, P < 0.05) but to a lesser extent than either GnRH (100 nM, 20.7-fold, P < 0.001) or phorbol-12-myristate-13-acetate (TPA, 100 nM, 8.7-fold, P < 0.05). The transcriptional response to a combination of BayK8644 and TPA was approximately additive. Despite stimulating alpha-subunit gene expression, BayK8644 had no effect on alpha-subunit secretion at 24 h, and co-addition of BayK8644 and TPA did not produce any further stimulation of alpha-subunit secretion (3.0-fold, P < 0.001) compared with TPA alone (3.2-fold, P < 0.001). Pretreatment of alpha T3-1 cells with the calcium channel blocker, nifedipine (1 microM for 5 min), essentially blocked GnRH-stimulated alpha-promoter activity without affecting GnRH-stimulated alpha-subunit release. In contrast, thapsigargin pretreatment (1 microM for 5 min), which depletes intracellular calcium stores, significantly reduced basal and GnRH-stimulated secretion without affecting the ability of GnRH to increase alpha-promoter activity. Incubation of alpha T3-1 cells in calcium-depleted media showed that the transcriptional response was dependent on extracellular calcium concentration, with maximum stimulation by GnRH seen at a calcium concentration of 1.7 mM. Deletion analysis indicated that sequences between -420 and -244 bp were involved in mediating the response to BayK8644. Constructs containing only upstream alpha-promoter sequences from -517 to -98 bp, fused to the heterologous thymidine kinase promoter, exhibited loss of responsiveness to BayK8644 below -298 bp. These upstream elements were also found to be important for basal expression of the alpha-promoter and for mediating the response to TPA but were distinct from GnRH responsiveness of the human promoter in alpha T3-1 cells. These studies suggest differential regulation of GnRH-stimulated alpha-subunit gene transcription and secretion by extracellular calcium influx and intracellular calcium mobilization. The transcriptional response to extracellular calcium influx is mediated through two or more elements between -420 and -244 bp, which are also involved in basal and TPA-stimulated expression of the alpha-subunit promoter.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Effect of different storage temperatures, sample collection procedures and immunoassay methods on osteocalcin measurement.

The apparent instability of measured osteocalcin has been reported as method-dependent and related to preanalytical variables such as storage temperature, and the use of anticoagulants and protease inhibitors. The aim of this study was to determine a sample collection procedure which minimised osteocalcin degradation. Blood samples from five normal individuals were collected with or without anticoagulants and protease inhibitors (heparin, EDTA, or heparin and aprotinin) and stored at 4 degrees C, -20 degrees C or -70 degrees C for up to 7 days, 28 days and 90 days respectively. Osteocalcin was measured by both a monoclonal EIA specific for intact osteocalcin and a bovine polyclonal RIA. Osteocalcin concentrations in serum and EDTA-treated samples significantly decreased by 40% (P < 0.001) with the ELISA and 72% (P < 0.001) with the RIA after 7 days storage at 4 degrees C. Similar falls were documented in these samples when stored at -20 degrees C and -70 degrees C and measured by the ELISA. Minimal changes in osteocalcin immunoreactivity were observed in either assay when heparin-treated plasma with or without aprotinin was stored at -20 degrees C or -70 degrees C for up to 90 days. The apparent instability of measured osteocalcin can be minimised using these conditions.

Adult↗
PubMed1995

Metabolic control of non-insulin-dependent diabetic patients undergoing cataract surgery: comparison of local and general anaesthesia.

We studied 40 elderly patients undergoing cataract surgery. Ten non-insulin-dependent diabetes mellitus (NIDDM) patients received standardized general anaesthesia, 10 NIDDM patients received local anaesthesia using retrobulbar block, 10 non-diabetic control patients received general anaesthesia and 10 non-diabetic controls received retrobulbar block. We measured sequential changes in blood glucose, lactate and beta-hydroxybutyrate, serum cortisol and insulin, and plasma non-esterified fatty acid concentrations until 4 h after operation. The results showed that in both general anaesthesia groups, NIDDM and control, blood glucose and serum cortisol concentrations increased significantly during surgery, before returning to normal by 4 h after operation; in both local anaesthesia groups, glucose and cortisol concentrations changed little during surgery. Serum insulin concentrations increased 30 min after operation to coincide with the peak of the glucose increase in the non-diabetic patients who received general anaesthesia, but no insulin response was seen in the diabetic general anaesthesia patients. Blood glucose and insulin concentrations increased in patients who received local anaesthesia (NIDDM and controls) when they ate after operation. The results show that cataract surgery under local anaesthesia provides improved metabolic control for the diabetic patient. Its use maintains glucose homeostasis, prevents the increases in cortisol and glucose which are seen under general anaesthesia and obviates the need for postoperative starvation.

Aged↗
PubMed1995

Hormonal effects of thoracic extradural analgesia for cardiac surgery.

We have investigated the hormonal and metabolic effects of thoracic extradural analgesia with bupivacaine in addition to sufentanil 20 micrograms kg-1 in nine patients undergoing coronary artery bypass surgery. A control group received general anaesthesia alone. The catecholamine response was inhibited for 24 h after surgery in patients who had received extradural analgesia, and the cortisol response was suppressed during cardiopulmonary bypass. Blood glucose values were unchanged until 24 h after surgery in the extradural group. There were no significant differences in cardiac index between the two groups of patients, although heart rate and mean arterial pressure decreased before surgery in patients who received extradural analgesia. The benefits of this technique in terms of a reduction in postoperative morbidity remain to be determined.

Adult↗
PubMed1995

A large volume spacer significantly reduces the effect of inhaled steroids on bone formation.

Inhaled steroids are increasingly advocated as first line treatment for mild asthma. Some studies suggest that inhaled steroids suppress bone formation as reflected by a fall in plasma osteocalcin. Spacers have been shown to increase the proportion of inhaled aerosol that is deposited in the lungs and to reduce the amount swallowed. We measured plasma osteocalcin levels to determine the effect on bone formation of inhaled beclomethasone dipropionate (BDP) with and without a 750 ml spacer in a double-blind, randomised, placebo-controlled, cross-over study. Twenty-six healthy male volunteers took BDP 500 micrograms (two puffs of Becloforte) together with two puffs of placebo, inhaled twice daily for seven days. One inhaler was taken directly while the other was inhaled through a 750 ml spacer. After a two week washout period, the inhalers were exchanged so that BDP was taken by the alternate route for a further seven days. Fasting plasma osteocalcin levels were measured at 09.00 h before and at the end of each week. After a week of BDP taken directly (without a spacer), osteocalcin levels fell from 11.8 (SEM 0.6) ng/ml to 9.5 (SEM 0.5) ng/ml (p < 0.001). After a week of BDP taken through a spacer, osteocalcin levels fell from 12.1 (SEM 0.5) ng/ml to 11.1 (SEM 0.5) ng/ml (p < 0.001). The fall in osteocalcin when a spacer was used was significantly less than when BDP was taken directly (p < 0.005). This is likely to be because the systemic effects on bone are caused by swallowed rather than inhaled BDP, and this is limited by the use of a spacer. Spacers should be more widely prescribed with inhaled steroids. Further prospective studies are indicated to evaluate whether spacers protect bone mass.

Administration, Inhalation↗