Biomedical subjects

J D Best

Publications and source records attributed to J D Best.

At least 73 records · Page 4Linked to original sources

PubMed1990

Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity.

Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemic effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemic effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU.kg-1.min-1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 +/- 5 mU/L (mean +/- SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 +/- 1.4 mumol.kg-1.min-1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Sl) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 +/- 0.1 vs. 1.7 +/- 0.2 min-1 x 10(2), NS; pre- vs. postinfusion Sl 8.4 +/- 2.3 vs. 11.8 +/- 3.7 min-1.mU-1.L x 10(4), P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Lymphocytic hypophysitis. The clinical spectrum of the disorder and evidence for an autoimmune pathogenesis.

Lymphocytic hypophysitis, a rare disease hitherto restricted to women, usually presents with symptoms of hypopituitarism in relationship to pregnancy. Two patients who developed pituitary insufficiency from lymphocytic hypophysitis are described. In the first, visual deterioration due to chiasmal compression from hypophysitis arising in ectopic pituitary tissue responded to bromocriptine and corticosteroids. In the second, an insidious onset of hypopituitarism occurred over 5 years in an elderly male. Combined HLA and complement typing confirmed that both patients shared MHC class I, II and III alleles. These class II and III alleles have been described in association with Hashimoto's thyroiditis and insulin-dependent diabetes mellitus (IDDM), both of which may be associated with antipituitary antibodies. The features of these two cases extend the known clinical and pathological spectrum of this disease and, through identifying a common immunogenetic background, provide a possible link between the previous associations of this disorder and autoimmune thyroid disease and IDDM.

Adult↗

PubMed1990

Practical application of methods for in vivo assessment of insulin secretion and action.

In vivo measurement of insulin sensitivity can be made using the glucose clamp technique or the intravenous glucose tolerance test (IVGTT) with minimal model analysis. The glucose clamp provides a direct, readily understandable measure of insulin action but is more demanding for investigators and subjects. Assessment of insulin secretion must be made by a separate test. The IVGTT is easier to perform but the data are more difficult to analyse and the value for insulin sensitivity is a derived rather than direct measure. As well as insulin sensitivity, glucose mediated glucose disposal and insulin secretion are measured by the IVGTT. In fact the IVGTT technique relies on adequate endogenous insulin secretion whereas the glucose clamp does not. The choice between these two techniques depends on the study to be performed and the available laboratory facilities.

Animals↗

PubMed1989

Effects of short-term pulsatile and continuous insulin delivery on glucagon secretion and insulin secretion and action.

In six normal nonobese subjects, hyperinsulinemic euglycemic clamps were performed during paired sequential two-hour intravenous (IV) insulin infusions separated by an hour washout period. Each infusion was either 32 mU/kg/h of continuous insulin (CI) or 75% of this dose as 40-second pulses delivered every 13 minutes (PI). Six studies were performed with each of the following sequences in random order: PI-CI, CI-PI, and CI-CI. Based on the initial infusions, the insulin-dependent fractional glucose disappearance rate (X) during pulsatile insulin delivery (3.0 +/- 0.4 min-1 X 10(2), n = 6) was 73% of that of the continuous infusions (4.1 +/- 0.3 min-1 X 10(2), n = 12). This ratio was similar to that of the measured time-averaged plasma insulin areas (PI = 24.7 +/- 3.8 v CI = 31.4 +/- 3.5 mU/L). There was an average 23% enhancement of insulin's hypoglycemic effect during the second 12 CI infusions compared with the 12 initial CI infusions (X = 5.1 +/- 0.5 v 4.1 +/- 0.3 min-1 X 10(2), P less than .05). There was no significant difference between the enhancing effects of PI and CI infusions on insulin action in the subsequent CI's (X = 4.9 +/- 0.9 for PI-CI v X = 5.3 +/- 0.2 min-1 X 10(2) for CI-CI). First infusion PI significantly (P less than .05) decreased plasma C-peptide levels (0.34 +/- 0.05 to 0.20 +/- 0.06 mumol/L), whereas CI did not (0.33 +/- 0.02 to 0.32 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Inferior petrosal sinus sampling in acromegaly.

In view of the diagnostic value of bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) in localising preoperatively the site of the microadenoma in pituitary dependent Cushing's disease, the clinical value of BSIPSS was evaluated in five acromegalic patients with equivocal or negative pituitary CT scans. Intersinus GH gradients were obtained for all patients (range 1.6-4.2) but in only one case was the gradient correctly localised to the side of the tumour. Gradients of several other pituitary hormones, particularly prolactin (range 1.6-4.0), also demonstrated gradients parallel to the GH intersinus gradients. Despite the paradoxical intersinus GH gradients, the surgeon was able to readily identify the tumour at the time of surgery. Thus BSIPSS is of little assistance to the surgeon for the preoperative radiological evaluation in acromegaly and these results caution against the universal adoption of the BSIPSS technique in the radiological assessment of all secretory pituitary microadenomas.

Acromegaly↗

PubMed1989

Alternative method for minimal model analysis of intravenous glucose tolerance data.

The minimal models of glucose-insulin kinetics were used to analyze sets of data obtained from human subjects and dogs during frequently sampled intravenous glucose tolerance tests (FSIGTs). Analysis of some data sets from both species resulted in poor identification of parameters. To improve the parameter resolution, the information base on which the parameters are estimated was enlarged. This was accomplished by incorporating into the analysis 1) glucose data obtained between 0 and 8 min of the FSIGT and some of the insulin data obtained prior to the insulin peak and 2) a second set of FSIGT data for each individual obtained during a physiological perturbation. As a result, data analysis was considerably enhanced, with parameter fractional standard deviation being routinely reduced to less than 0.5. Analysis of stimulated data with noise levels for glucose and insulin set between 0.05 and 0.15 confirmed the improvement in parameter estimates. This modified approach to analysis of FSIGTs therefore consistently leads to well-defined kinetic descriptions of experimental data in various situations and supports the usefulness of the minimal model in examining the complex interplay between the parameters that influence overall glucose tolerance.

Adult↗

PubMed1989

Familial acromegaly.

Five family members over 3 generations had isolated functional pituitary adenomas diagnosed. In four cases acromegaly was diagnosed, and in the fifth galactorrhoea from prolactin excess was the presenting feature. A prominent feature of the affected members tumours were histological finding of either atypical mixed cell or undifferentiated cell type. Given the low incidence of acromegaly and the demonstration of vertical transmission over 3 generations it is suggested this family represents an inherited pituitary syndrome, distinct from Multiple Endocrine Neoplasia (MEN) type 1.

Acromegaly↗

PubMed1989

Fenfluramine increases insulin action in patients with NIDDM.

These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently sampled intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a significant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 +/- 1.2 vs. 8.4 +/- 0.89 mM, mean +/- SE, P less than .01) with no significant fall in fasting serum insulin (20 +/- 2 vs. 24 +/- 3 microU/ml) or C-peptide (1.3 +/- 0.2 vs. 1.3 +/- 0.1 nM). During euglycemic-hyperinsulinemic (1 mU.kg-1.min-1) clamp studies there was a significant increase in insulin action from 12.7 +/- 2.3 to 17.3 +/- 1.8 min-1.10(3) microU.ml-1 (P less than .05), although clamp insulin levels were lower after fenfluramine treatment (136 +/- 14 vs. 96 +/- 9 microU/ml, P less than .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 +/- 1.5 vs. 20.1 +/- 2.1 ml.kg-1.min-1, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Hormonal effects of norepinephrine on acute glucose disposal in humans: a minimal model analysis.

It is not known whether circulating norepinephrine (NE) has a direct hormonal influence on glucose disposal. This study examines whether moderate elevation of NE alters the disposal of an acute intravenous (IV) glucose load, as analysed by the minimal model of Bergman. Eight healthy normal subjects were infused with either 25 ng/kg/min NE (plasma NE 1,284 +/- 259 pg/mL) or normal saline (plasma NE 314 +/- 86 pg/mL), 30 minutes prior to and during an IV glucose tolerance test (GTT). There was a small but significant rise (P less than .05) in basal blood glucose levels during the initial 30-minute NE infusion which was accompanied by a 40% increase (0.39 +/- .02 to 0.59 +/- .07 nmol/L, P less than .01) in nonesterified fatty acid levels (NEFA). Insulin, C-peptide, and glucagon levels did not change. NE impaired the rate of acute glucose disposal (Kg 1.74 +/- 0.24 v 2.10 +/- 0.23 (min-1, P less than .05). Minimal model analysis revealed a corresponding 35% decrease in insulin sensitivity (SI 4.85 +/- 1.51 v 7.28 +/- 1.16 min-1 microU-1 mL-1 x 10(4), P less than .05) but no significant differences between glucose-mediated glucose disposal or pancreatic B-cell responsiveness. The glucose disposition index (si* phi2), a direct measure of an individual's overall insulin- mediated glucose disposal, was reduced by 70% in the NE-infussed subjects (si* phi2 69 +/-22 v 223 +/- 76 mg-1 ml-1 min-3 x 10(2), p< .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Clinical spectrum of primary empty sella turcica.

Over recent years empty sella turcica has become more frequently diagnosed with high resolution computerized tomography and the associated clinical abnormalities have been better described. In this article the spectrum of clinical presentation is based on a review of 26 cases with six illustrative case reports. Recommendations for management and further assessment are presented. It is important for clinicians to be aware of the varying presentations of this syndrome, since it should not be considered simply as an incidental finding. A patient diagnosed with empty sella syndrome requires clinical and endocrine evaluation, and appropriate follow-up as determined by initial test results.

Adult↗

PubMed1988

Hormonal and metabolic changes during hypothermic coronary artery bypass surgery in diabetic and non-diabetic subjects.

Hormonal and metabolic responses to hypothermic coronary artery bypass grafting (CABG) were studied in three groups: 8 non-diabetic patients, 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) given a glucose pump priming solution and 8 NIDDM patients given a non-glucose infusion. There were no significant differences in stress hormone responses between NIDDM and non-diabetic patients, with adrenaline concentrations rising 10-fold, noradrenaline 4-fold and cortisol 2 to 3-fold. Glucagon rose significantly during bypass only in the NIDDM patients who did not receive a glucose prime. Comparable marked hyperglycaemia was seen in both glucose primed groups during bypass and exclusion of glucose from the prime in NIDDM patients prevented this major rise. Postoperatively, the rise in insulin in the glucose primed NIDDM patients contrasted with the slower rise in the non-glucose primed NIDDM patients who were also hyperglycaemic by this stage. Perioperative hyperglycaemia in NIDDM patients undergoing CABG can be prevented by using a non-glucose priming solution and by giving insulin infusion, particularly postoperatively.

Blood Glucose↗

PubMed1988

Effects of epinephrine infusion on determinants of intravenous glucose tolerance in dogs.

Effects of four- to fivefold elevations of epinephrine (EPI) on glucose (Glc) metabolism were assessed in eight dogs before and after an intravenous Glc tolerance test, performed 30 min (short EPI) and 72 h (long EPI) after start of EPI infusion. Short EPI increased plasma nonesterified fatty acids (NEFA; 0.46 +/- 0.08 to 0.78 +/- 0.12 mmol/l, P less than 0.05), but Glc and insulin were unchanged. After long EPI, NEFA returned to control but Glc increased from 5.1 +/- 0.1 to 5.7 +/- 0.2 mmol/l (P less than 0.05). EPI reduced overall Glc tolerance (KG) from 3.5 +/- 0.7 to 2.5 +/- 0.2 (short EPI, P less than 0.05) and 2.3 +/- 0.3%/min (long EPI, P less than 0.02). Minimal model analysis showed that short EPI decreased insulin sensitivity (SI) from 7.9 +/- 1.1 to 4.2 +/- 1.2 min-1 per mU/l X 10(-4) (P less than 0.005) and increased pancreatic responsiveness (phi 1 from 3.7 +/- 0.3 to 7.4 +/- 2.9 mU/l.min-1 per mg/dl, P less than 0.025; phi 2 from 2.6 +/- 0.7 to 4.9 +/- 1.2 mU/l.min-2 per mg/dl). After long EPI SI, phi 1, and phi 2 returned to control. In contrast, Glc-mediated Glc disposal (SG) was decreased from 3.5 +/- 0.5 X 10(-2) to 2.8 +/- 0.6 X 10(-2) (short EPI) and 1.3 +/- 0.6 X 10(-2) min-1 (long EPI, P less than 0.02). We conclude that prolonged infusion of EPI leads to adaptation to its acute effects on NEFA, SI, phi 1, and phi 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Multiple pituitary hormone gradients from inferior petrosal sinus sampling in Cushing's disease.

Pre-operative bilateral simultaneous inferior petrosal sinus sampling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients greater than or equal to 1.4:1 were seen for beta-endorphin (2.8 +/- 1.3, mean +/- SEM), PRL (4.2 +/- 1.3) and GH (6.9 +/- 2.4) as well as for ACTH (5.1 +/- 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and beta-endorphin were r = 0.95 (P less than 0.01), ACTH and PRL r = 0.90 (P less than 0.01) and for ACTH and GH r = 0.89 (P less than 0.05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to co-secretion of beta-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of beta-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus sampling can give information about pituitary function unobtainable from peripheral hormone levels.

Adolescent↗

PubMed1987

The clinical effects of mixing short- and intermediate-acting insulins in the treatment of non-insulin-dependent diabetes.

Premixing short- and intermediate-acting insulins in one syringe, with refrigerated storage before injection, is practised by some centres in the treatment of older patients with non-insulin-dependent diabetes. Because other studies have reported the loss of the short-acting insulin component after mixing with intermediate-acting insulins, we examined the clinical effect of mixing soluble insulin with lente or isophane insulins in subjects with non-insulin-dependent diabetes. When soluble and lente insulins were mixed in the same syringe and injected immediately, the peak level of insulin was very similar to the peak level after separate injections but occurred at five hours instead of three hours after the injection. As a result, the plasma free-insulin profile over three hours was lower with premixed insulin than after separate injections of the two insulins (incremental insulin area, 88 +/- 20 mU.L-1.h, and 129 +/- 37 mU.L-1.h, respectively; P less than 0.05). This delay in the absorption of soluble insulin caused a greater rise in plasma glucose levels such that the incremental glucose area over eight hours was 25.5 +/- 4.4 mmol.L-1.h for premixed insulin compared with 10.4 +/- 6.2 mmol.L-1.h for separate injections (P less than 0.05). Soluble and isophane insulins had similar absorption profiles whether injected separately or premixed (incremental insulin area, 0 to 3 h, 176 +/- 44 mU.L-1.h and 156 +/- 29 mU.L-1.h, respectively). Our results indicate that the absorption of soluble insulin is delayed when it is mixed with lente insulin but not with isophane insulin. Even in subjects with endogenous insulin secretion, this effect may have clinical importance and should be taken into account when insulin therapy is adjusted for patients with non-insulin-dependent diabetes.

Absorption↗

PubMed1987

Halothane anesthesia does not suppress sympathetic activation produced by neuroglucopenia.

To determine the suitability of halothane anesthesia for studies of sympathetic control of the endocrine pancreas in dogs, we assessed the effect of halothane anesthesia (0.8% inspired concentration) on the sympathetic response to central neuroglucopenia. In dogs anesthetized with halothane, intravenous administration of the neuroglucopenic agent, 2-deoxy-D-glucose (2-DG; 100 mg/kg), produced increases of both systemic plasma epinephrine (EPI; delta = 269 +/- 86 pg/ml, P less than 0.025) and norepinephrine (NE; delta = 157 +/- 55 pg/ml, P less than 0.025) equivalent to those previously observed in conscious dogs. Measurement of plasma NE kinetics revealed that the plasma NE response to 2-DG during halothane was due to an increase in the rate of NE appearance that was identical to that of conscious dogs, rather than to an impairment of NE clearance. In contrast, 2-DG at this dose did not increase plasma EPI or NE levels in dogs anesthetized with pentobarbital sodium (30 mg/kg). Plasma glucose increased modestly after 2-DG (100 mg/kg) in both conscious and halothane-anesthetized dogs but not in the pentobarbital-anesthetized dogs. Although 2-DG at a threefold higher dose (300 mg/kg) caused plasma EPI, NE, and glucose (delta = 12 +/- 3 mg/dl, P less than 0.001) to increase in pentobarbital-anesthetized dogs, the responses to this higher dose of 2-DG were all significantly larger in halothane-anesthetized dogs (delta of plasma glucose = 30 +/- 8 mg/dl, P less than 0.005; P less than 0.0025 vs. pentobarbital).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Metabolic consequences of prolonged hyperinsulinemia in humans. Evidence for induction of insulin insensitivity.

Hyperinsulinemia is frequently associated with a variety of insulin-resistant states and has been implicated causally in the development of insulin resistance. This study examines the metabolic consequences of prolonged hyperinsulinemia in humans. Basally and 1 h after cessation of a 20-h infusion of insulin (0.5 mU X kg-1 X min-1, aimed at elevating plasma insulin levels to approximately 30 mU/L) or normal saline, subjects were assessed for glucose turnover with 3-[3H]glucose; insulin sensitivity, as measured by either the euglycemic glucose-clamp technique or the intravenous glucose tolerance test (IVGTT) minimal model method of Bergman; and monocyte insulin-receptor binding. Hepatic glucose production (Ra) was suppressed by greater than 95% during each euglycemic clamp and during the 20-h insulin infusion. After the insulin infusion, Ra and glucose utilization rate returned to the initial basal level within 1 h, as did insulin levels. At that time, insulin sensitivity was significantly decreased, as measured by the "insulin action" parameter during the 40- to 80-min phase of the clamp (0.049 +/- 0.003 vs. 0.035 +/- 0.007 min-1, P less than .05) and during the 80- to 120-min phase (0.047 +/- 0.005 vs. 0.039 +/- 0.007 min-1, .05 less than P less than .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

Glucose regulation in non-insulin-dependent diabetes mellitus. Interaction between pancreatic islets and the liver.

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.

Arginine↗

PubMed1985

Phaeochromocytoma: a review of the St Vincent's Hospital, Melbourne experience (1969-84) and of recent advances in management.

Phaeochromocytoma is an unusual tumour which is eminently curable by surgical means. It is difficult to diagnose clinically because it mimics other illnesses. The clinical features of 13 cases of phaeochromocytoma diagnosed at St Vincent's Hospital, Melbourne, between 1969 and 1984 are briefly described. This review emphasizes the several major improvements in both diagnostic and localizing tests which have occurred over the 16 year period of the series. These include the clonidine suppression test and plasma and urine catecholamine estimations in diagnosis and techniques such as CT scanning and the I131-meta-iodobenzyl-guanidine scan used for localization of the tumour. Careful pre-operative preparation, based on adequate alpha blockade and intra-operative monitoring, is essential for the safe and successful removal of the tumour, which was eventually accomplished for all 12 cases in which removal was attempted. However, the most important step in the diagnosis and treatment of phaeochromocytoma is the initial consideration of the diagnosis. This step depends on the level of awareness of the disorder amongst clinicians.

Adrenal Gland Neoplasms↗