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Biomedical subjects

M Nattrass

Publications and source records attributed to M Nattrass.

At least 55 records · Page 3Linked to original sources
PubMed1991

Working towards dependency scoring in critical care.

One of the main disadvantages of dependency scoring in the intensive care unit, is that popular scoring systems such as the Intensive Care Register (ICR) fail to take into account many of the most important factors that contribute to patient dependency. Factors such as counselling of patients and their families, setting up for certain procedures and dealing with an agitated patient, for example, all contribute to the overall dependency of the patients; and ultimately influence the level of nursing support required. It is with these thoughts in mind that a system of dependency scoring has been developed for the intensive care unit (ICU). The system outlined here is designed to be used in conjunction with the ICR, thus providing a more accurate and realistic measure of dependency; while still maintaining a vital link to a well established system.

Consciousness↗
PubMed1991

Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma.

Twelve-hour hormonal and metabolic profiles were performed in a 68-year-old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha-blockade with phenoxybenzamine, (c) after combined alpha and beta-blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12-h mean +/- SD) were observed in the concentrations of noradrenaline (44.9 +/- 14.4 vs 2.3 +/- 0.7 nmol/l, P less than 0.01), glucose (6.9 +/- 1.9 vs 5.0 +/- 1.0 mmol/l, P less than 0.05), glycerol (0.22 +/- 0.02 vs 0.07 +/- 0.01 mmol/l, P less than 0.01), non-esterified fatty acids (0.71 +/- 0.28 vs 0.34 +/- 0.08 mmol/l, P less than 0.01), and total ketone bodies (0.08 +/- 0.03 vs 0.03 +/- 0.02 mmol/l, P less than 0.01). Alpha-blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P less than 0.01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta-blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12-h blood glucose profile, however, was observed only post-operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Impaired glucose tolerance in obesity is associated with insensitivity to insulin in multiple aspects of metabolism as assessed by a low dose incremental insulin infusion technique.

To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty-two obese subjects were studied by low-dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9-80.9 kg m-2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8-21.6) (-SD(-)+SD) vs 9.6 (6.4-14.5) mU l-1, p less than 0.01) and during the infusion (p less than 0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2 +/- 0.8 (+/- SE) vs 18.9 +/- 2.1 ml kg-1 min-1, p less than 0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3 +/- 0.4 vs 4.5 +/- 0.6 mol kg-1 min-1, p less than 0.02) and remained elevated during infusion (p less than 0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022 +/- 0.010 vs 0.047 +/- 0.017 ml kg-1 min-1 mU-1 l, p less than 0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose-response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non-esterified fatty acids 0.72 (95% CI 0.62-0.84) and glycerol 1.85 (1.37-2.49).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Impaired glucose tolerance is characterized by multiple abnormalities in the regulation of intermediary metabolism.

The responses of circulating intermediary metabolites to a low-dose sequential insulin infusion (basal, 0.005, 0.01, and 0.05 U kg-1 h-1) were assessed in eight non-obese men with Impaired Glucose Tolerance (IGT), and in eight healthy control subjects with normal glucose tolerance matched for age, gender, and body mass index. Fasting hyperinsulinaemia was observed in the subjects with IGT (7.4 +/- 1.0 vs 2.9 +/- 0.3 mU I-1, p less than 0.001). While there was no significant difference (p greater than 0.1) in fasting venous glucose levels between the groups, fasting concentrations of lactate (p less than 0.02), alanine (p less than 0.01), and glycerol (p less than 0.05) were significantly elevated in the subjects with IGT. During the incremental insulin infusion, overall concentrations of glucose (p less than 0.05), lactate (p less than 0.05), alanine (p less than 0.05), glycerol (p less than 0.05), immunoreactive insulin (p less than 0.001), and C-peptide (p less than 0.01) were significantly higher in the subjects with IGT. Linear dose-response relationships (p less than 0.005) for circulating immunoreactive insulin (log) vs metabolite concentrations were demonstrated by analysis of variance for glucose, non-esterified fatty acids (NEFA), glycerol, and total ketone bodies. For glucose, glycerol, and NEFA, group dose-response regression lines for the subjects with IGT were displaced significantly to the right (p less than 0.001 for each) of those for the normal control subjects, implying insulin insensitivity. In addition to the recognized defect in glucose homeostasis, these results indicate impaired regulation of multiple aspects of intermediary metabolism including lipolysis in IGT.

Alanine↗
PubMed1991

The short-term effect of nicotinic acid on intermediary metabolism in insulin-dependent diabetes mellitus.

The short-term effect of the lipid lowering agent nicotinic acid on circulating concentrations of insulin, glucose, lactate, pyruvate, non-esterified fatty acids (NEFA), glycerol, total ketone bodies and triglycerides was examined in six insulin-dependent diabetic patients. On two occasions a week apart 24h metabolic profiles were performed. Three patients received nicotinic acid (800 mg/day) for 1 week prior to the first study and three patients between studies. Using this dose of nicotinic acid in patients with insulin-dependent diabetes no lipid lowering effect was demonstrated, nor did we observe an impairment of glycaemic control. During treatment with nicotinic acid circulating free insulin concentrations were higher and blood glucose concentrations were lower. Despite the higher insulin concentrations, circulating levels of NEFA, ketone bodies, and glycerol were all significantly elevated during treatment with nicotinic acid. These results suggest that any extrapolation of findings with regard to the use of nicotinic acid and its derivatives in non-insulin-dependent diabetes to insulin-dependent diabetes should be considered with caution.

Adult↗
PubMed1991

Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance.

The published literature on the influence of obesity on intermediary metabolite concentrations does not adequately address the potential confounding effects of the increased prevalence of impaired glucose tolerance in obese subjects. In order to remove this, we studied 109 subjects with proven normal glucose tolerance ranging from underweight to grossly obese (range 15.3-80.9 body mass index). All had blood intermediary metabolites, plasma insulin and C-peptide measured after an overnight fast. Thirty-six (18 from each end of the range of body mass index) received a 3-hour oral glucose tolerance test for metabolites and insulin. Fasting plasma insulin was highly significantly associated with body mass index (r = 0.72; P less than 0.001). Concentrations of lipid intermediaries were better associated with body mass index than with fasting plasma insulin: non-esterified fatty acids (r = 0.36; P less than 0.001), glycerol (r = 0.47; P less than 0.001) and ketone bodies (r = 0.45; P less than 0.001). Fasting concentrations of carbohydrate intermediaries were, however, better correlated with fasting plasma insulin: lactate (r = 0.29; P less than 0.01), pyruvate (r = 0.24; P less than 0.01) and alanine (r = 0.36; P less than 0.001). Glucose concentrations were associated with both to a similar degree (r = 0.33, r = 0.32, respectively; P less than 0.001). After oral glucose, exaggerated rises in plasma insulin and blood glucose were observed in obese subjects but a lesser rise was seen for lactate. Non-esterified fatty acids and ketones, although having higher fasting concentrations in obese subjects, fell to similar concentrations in the two groups after glucose whereas blood glycerol did not fall so far in the obese subjects. The results suggest, even if those subjects with impaired glucose tolerance are excluded, insensitivity to insulin in several aspects of intermediary metabolism in obesity the degree of which may vary in different metabolic pathways or tissues.

Adult↗
PubMed1991

Abnormal regulation of carbohydrate metabolism in motor neurone disease.

In this study, circulating concentrations of intermediary metabolites were measured in eight non-obese subjects with motor neurone disease in the basal (postabsorptive) state, and after a 75 g oral glucose challenge. Eight healthy subjects of similar age and body mass index served as controls. Basal pyruvate concentration was significantly elevated in the subjects with motor neurone disease (p less than 0.02). After oral glucose ingestion, overall levels of pyruvate (p less than 0.01) and lactate (p less than 0.05) were significantly higher in these subjects. Blood glucose concentrations fulfilled the criteria diagnostic of impaired glucose tolerance in six of the eight subjects with motor neurone disease (WHO, 1985). Cumulative insulin levels were slightly higher in these subjects and peak insulin response was delayed (120 min vs. 60 min) relative to the healthy controls. Circulating concentrations of alanine, glycerol, non-esterified fatty acids and total ketone bodies were similar between groups. These results confirm that impaired glucose tolerance is a common feature of motor neurone disease. Furthermore, our data indicate disordered regulation of both pyruvate and lactate metabolism, consistent with reports of defective skeletal muscle pyruvate oxidation in individuals with this disorder. In contrast, our results indicate that the regulation of lipolysis and ketone body metabolism is unimpaired in motor neurone disease.

Alanine↗
PubMed1990

Abnormal regulation of intermediary metabolism after oral glucose ingestion in myotonic dystrophy.

The responses of plasma insulin and blood intermediary metabolites to oral glucose (75 g) were determined in 10 subjects with myotonic dystrophy. Results were compared with responses in 10 normal control subjects matched for age, sex, and body mass index. Fasting hyperinsulinemia was observed in the myotonic subjects (7.5 +/- 1.6 v 2.4 +/- 0.4 mU/L; P less than .005) and plasma insulin concentration remained significantly higher following oral glucose (F = 38.09; P less than .001). Total cumulative insulin release was markedly higher in the myotonic subjects (4,984.3 v 1,286.6 mU/L; P less than .0001). Basal blood glucose concentration was normal (4.8 +/- 0.2 v 4.7 +/- 0.1 mmol/L), although overall blood glucose was elevated in the myotonic subjects following oral glucose ingestion (F = 5.37; P less than .05). Glucose tolerance was normal in all subjects. Fasting blood lactate was higher in the myotonic subjects (1.31 +/- 0.13 v 0.94 +/- 0.08 mmol/L; P less than .05) and remained significantly elevated following the ingestion of glucose (F = 7.22; P less than .02). Blood pyruvate response was also higher in the myotonic subjects (F = 5.88; P less than .05). Basal blood glycerol was elevated in the myotonic subjects (0.12 +/- 0.02 v 0.05 +/- 0.01 mmol/L; P less than .005) and remained elevated following oral glucose (F = 11.31; P less than .005). No significant overall differences were observed in ketone bodies, alanine, or fatty acids between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Metabolic abnormalities in obese patients with impaired glucose tolerance.

It is not clear whether the glucose tolerance test diagnosis of Impaired Glucose Tolerance introduced in the recent revisions of diagnostic criteria is associated with abnormalities of intermediary metabolism other than glucose. Intermediary metabolite concentrations have therefore been studied fasting and in response to oral glucose in 35 patients referred with morbid obesity accompanied by either normal glucose tolerance (18 patients) or Impaired Glucose Tolerance (17 patients). When fasting obese patients with Impaired Glucose Tolerance had significantly higher blood total ketone body concentrations, 0.24 (0.19-0.30) vs 0.14 (0.12-0.16) mmol l-1 (antilog of mean-SE to mean + SE) (p less than 0.05), and lower blood glycerol concentrations, 0.14 +/- 0.01 vs 0.18 +/- 0.01 mmol l-1 (mean +/- SE) (p less than 0.05), than obese patients with normal glucose tolerance. There were no significant differences in fasting insulin, 16 (15-18) vs 14 (12-15) mU l-1, or glucose levels, 5.3 +/- 0.2 vs 5.1 +/- 0.2 mmol l-1. After oral glucose there was an exaggerated rise in glucose, insulin, lactate, and pyruvate in patients with Impaired Glucose Tolerance.

Adult↗
PubMed1990

Changing sex ratio in diabetic ketoacidosis.

An annual audit of diabetic ketoacidosis and hyperosmolar non-ketotic state was made in one hospital from 1971 to 1988. There were 846 episodes of ketoacidosis and 126 episodes of hyperosmolar state. A relative fall occurred in the number of episodes of ketoacidosis compared with hyperosmolar state over this time (p less than 0.05), and there was a change of female:male ratio for episodes of ketoacidosis occurring in established diabetes from 2.79 to 1.59 (p less than 0.01). In contrast the female:male ratio remained unchanged (mean 1.16) for episodes of hyperosmolar state and remained less than 1.0 for all episodes of ketoacidosis in previously undiagnosed diabetes mellitus. Among patients who suffered recurrent ketoacidosis there was a reduction in the number of episodes occurring in female patients and an increase in the number of episodes occurring in male patients in each successive 6-year period with consequent change in female:male ratio for this subgroup from 7.33 to 4.75 to 1.12 (p less than 0.001).

Adolescent↗
PubMed1989

Use of combined oral contraceptive preparations alters the insulin sensitivity of fatty acid and ketone metabolism.

Eight women taking low-dose-oestrogen combined oral contraceptive preparations were compared to eight women in the luteal phase of the menstrual cycle during hourly incremental insulin infusions of 0 (basal), 0.005, 0.01 and 0.05 U/kg/h short-acting insulin. Dose-response relationships between insulin and intermediary metabolites were sought by analysis of variance applied to regression. For insulin (log) and glucose the slope of the relationship was significantly shallower in the oral contraceptive group. For insulin (log) and non-esterified fatty acids the slopes of the regression lines were not different between groups but lines were significantly displaced. For insulin (log) and total ketone bodies (log) slopes of the regression lines were not different but significant displacement was observed. At identical insulin concentrations women taking an oral contraceptive had higher non-esterified fatty acids (NEFA) (difference between groups +0.15 mmol/l, P less than 0.001) and total ketone bodies (log: -0.26 mmol/l, P less than 0.001). The potency of insulin action in oral contraceptive users versus the luteal group was 0.47 (P less than 0.01) for NEFA and 0.38 (P less than 0.001) for total ketone bodies. The results demonstrate, for the first time, in-vivo insulin resistance of NEFA and ketone bodies' metabolism induced by oral contraceptive use.

Adult↗
PubMed1989

Metabolic profiles in patients with insulinoma.

Twelve-hour metabolic profiles have been measured in six patients with insulinoma and results compared with normal subjects of similar age and weight. Fasting blood glucose was lower (mean +/- SEM 2.9 +/- 0.3 mmol/l vs 5.0 +/- 0.2 mmol/l) and plasma insulin higher (20.0 +/- 3.9 mU/l vs 7.2 +/- 1.6 mU/l) in insulinoma patients. Over the 12-h period blood glucose, pyruvate and glycerol were significantly lower, and plasma insulin, blood lactate, alanine and plasma non-esterified fatty acids (NEFA) significantly higher in insulinoma patients. Overall the concentration of blood total ketone bodies was significantly higher in insulinoma patients. Values were higher in the early part of the day but lower later in the day and did not show the marked pre-meal rise observed in the normal subjects. The raised NEFA and ketone bodies are of particular interest as they may be a source of fuel supply in the presence of relative glucose deficiency.

Adenoma, Islet Cell↗
PubMed1989

Xiaoke tea, a Chinese herbal treatment for diabetes mellitus.

Xiaoke tea, a traditional Chinese treatment for diabetes mellitus, lowered blood glucose concentrations in streptozotocin diabetic mice. To investigate Xiaoke clinically, a double-blind crossover study was undertaken in 12 non-insulin-treated diabetic patients. Xiaoke tea and ordinary tea (infusion of 2.72 g, 4 times daily) were consumed in random order for 4 weeks. A standard breakfast meal was taken before and after each treatment period. Xiaoke did not significantly affect glycosylated haemoglobin, basal or post-breakfast serum glucose and insulin concentrations, intermediary metabolite concentrations, triglyceride and cholesterol. No adverse side-effects of Xiaoke were evident.

Blood Glucose↗
PubMed1989

The metabolic effects of fatal cyanide poisoning.

Metabolic and toxicological data were obtained during the first 24 hours following severe and eventually fatal cyanide poisoning. Initial blood cyanide concentrations were 804 mumol/l but fell rapidly over 24 hours following cobalt edetate therapy to 15 mumol/l. However, plasma thiocyanate concentrations rose over 24 hours (147-267 mumol/l) suggesting continued tissue detoxification. The major metabolic abnormality was lactic acidosis (initial pH 7.21, blood lactate 17.5 mmol/l) which corrected over 12 hours. Despite high circulating insulin concentrations the responses of blood glucose, plasma non-esterified fatty acid, blood glycerol and 3-hydroxybutyrate suggested marked insulin resistance.

Acidosis, Lactic↗
PubMed1989

Variability of three standard neurophysiological techniques in established symptomatic diabetic polyneuropathy.

The reproducibility of three standard neurophysiological techniques (motor and sensory nerve conduction velocities, vibration perception threshold and mean expiratory: inspiratory electrocardiographic R-R ratio) was determined from duplicate measurements approximately four weeks apart in 50 patients with chronic symptomatic diabetic polyneuropathy. There was no change in average glycaemic control (mean +/- SD) between the measurements (HbA1 10.7 +/- 2.0 vs. 10.4 +/- 2.1% at zero and four weeks respectively). While there were no significant differences in the mean values at zero and four weeks for any technique considerable intra-individual variability was observed in several measurements. Mean coefficients of variation (CV) for motor nerve conduction velocity ranged from 9.8% (ulnar nerve) to 10.7% (median) to 12.2% (peroneal nerve). Variability in sensory nerve conduction velocities (CVs 8.6, 8.7 and 14.7% for radial, ulnar and sural nerves respectively) was complicated by a high proportion of unrecordable action potentials. Duplicate action potentials were recordable from the sural nerve in only 15 (30%) patients. The highest intra-individual variability was observed in measurements of vibration perception threshold with CVs of 21.0% (thumb) and 18.0% (hallux). The apparently satisfactory CV of 3.6% for the cardiac E:I ratio test may represent an artefactually low degree of variability. Neurophysiological techniques in current use are characterized by technical limitations and intra-individual variability in patients with established diabetic neuropathy.

Blood Glucose↗