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Biomedical subjects

I A MacDonald

Publications and source records attributed to I A MacDonald.

At least 19 recordsLinked to original sources
PubMed2006

Urinary catecholamine excretion in tetanus.

Imperfect understanding of the pathophysiology of tetanus has limited therapeutic advances. Autonomic disturbance is a major cause of mortality and is believed to be associated with catecholamine release, predominantly norepinephrine. We measured epinephrine and norepinephrine concentrations in 24-h urine collections from tetanus and critically ill patients suffering from other severe diseases. In patients with severe tetanus, mean (SD) epinephrine was 164.18 (129.37) nmol x day(-1) compared with 45.18 (37.74) nmol x day(-1) in mild-moderate disease (p = 0.008). In the severe group, mean (SD) norepinephrine was 411.64 (208.5), and 121.00 (81.81) nmol x day(-1) in moderately ill patients (p < 0.001). Compared with critically ill control patients, median epinephrine was 331.77 in tetanus patients and 89.70 nmol x day(-1) in controls (p < 0.001). Median norepinephrine concentration was 788.02 nmol x day(-1) in tetanus and 300.05 nmol x day(-1) in control patients, p = 0.006. The study finds a novel result of increased epinephrine excretion in tetanus and confirms that catecholamine excretion in tetanus exceeds that in other critically ill patients. These results should be considered in designing more effective therapeutic strategies.

APACHE↗
PubMed2004

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes. METHODS: We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7-18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 min for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia. RESULTS: Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA(1)c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/l, p=0.0003) and were inversely correlated with maximum QTc (r=-0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc. CONCLUSIONS/INTERPRETATION: In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia.

Adolescent↗
PubMed2000

Hypoglycaemic counter-regulation at normal blood glucose concentrations in patients with well controlled type-2 diabetes.

BACKGROUND: Intensive treatment to achieve good glycaemic control in diabetic patients is limited by a high frequency of hypoglycaemia. The glucose concentrations at which symptoms and release of counter-regulatory hormones takes place have not been studied in patients with well controlled type-2 diabetes. METHODS: We studied seven well controlled, non-insulin treated, type-2 diabetic patients (mean HbA1c [corrected according to Diabetes Control and Complications Trial] 7.4%, SD 1.0) and seven healthy controls matched for age, sex, and body mass index with a stepped hyperinsulinaemic hypoglycaemic glucose clamp. Symptoms, cognitive function, and counter-regulatory hormone concentrations were measured at each glucose plateau, and the glucose value at which there was a significant change from baseline was calculated. FINDINGS: Symptom response took place at higher whole-blood glucose concentrations in diabetic patients than in controls. Counter-regulatory release of epinephrine, norepinephrine, growth hormone, and cortisol showed a similar pattern--eg, at blood glucose concentrations of 3.8 mmol/L [SD 0.4] vs 2.6 [0.3] for epinephrine. INTERPRETATION: Glucose thresholds for counter-regulatory hormone secretion are altered in well controlled type-2 diabetic patients, so that both symptoms and counter-regulatory hormone release can take place at normal glucose values. This effect might protect type-2 diabetic patients against episodes of profound hypoglycaemia and make the achievement of normoglycaemia more challenging in clinical practice.

Adult↗
PubMed1999

Suppression of the nocturnal rise in growth hormone reduces subsequent lipolysis in subcutaneous adipose tissue.

BACKGROUND: The aim of this study was to examine the effect of the nocturnal rise in growth hormone (GH) concentration on lipolysis in adipose tissue the following morning. METHODS: Eight healthy subjects were studied on two occasions (control vs. suppression of GH secretion) and six were studied on a third occasion (control vs. replacement of GH). Lipolysis in the whole body was assessed by measurement of systemic glycerol turnover. Lipid metabolism in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences. RESULTS: Suppression of the nocturnal rise in GH did not affect systemic glycerol turnover. However, in subcutaneous abdominal adipose tissue it led to a significant reduction in the veno-arterial differences in nonesterified fatty acid (NEFA, P = 0.041) and glycerol (P = 0. 014) concentrations, reflecting a reduction in intracellular lipolysis (P = 0.011). Although arterialized plasma triacylglycerol (TG) concentrations were reduced in the absence of the nocturnal GH pulse, the extraction of TG in subcutaneous abdominal adipose tissue remained unchanged. CONCLUSION: We conclude that the normal nocturnal rise in plasma GH concentration leads to site-specific regulation of lipolysis in adipose tissue on the following day, with preferential fat mobilization from central depots.

Adipose Tissue↗
PubMed1998

Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin-dependent diabetes mellitus.

1. Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in healthy volunteers. This study examines whether this also occurs in insulin-dependent diabetes. Changes in four-choice reaction time, auditory brain stem response, and P300 latency were used as measures of cerebral function. 2. Ten subjects were studied twice at least 4 weeks apart. Blood glucose was maintained between 5 and 8 mmol/l for 1 h before starting a 60 m-unit min-1 m-2 stepped hyperinsulinaemic clamp, achieving blood glucose concentrations of 4.5, 3.3 and 2.5 mmol/l. At one visit, 40 mumol min-1 kg-1 sodium lactate was infused, and at the other, normal saline. Cerebral function was measured at each blood glucose concentration. 3. Blood lactate rose to 3.32 +/- 0.06 mmol/l during lactate infusion compared with 0.9 +/- 0.03 mmol/l during saline infusion. Compared with the results at 4.5 mmol/l there were no significant changes at 3.3 mmol/l in any measure of cerebral function at either visit. At 2.5 mmol/l a significant increase in reaction time and P300 latency occurred with saline [mean change 33.1 +/- 8.6 ms (P < 0.01) and 30.1 +/- 9.2 ms (P < 0.01) respectively] but not lactate [mean change -5.9 +/- 3.7 ms (P > 0.05) and -6 +/- 7.6 ms (P > 0.05) respectively]. No significant changes occurred in auditory brain stem response. The catecholamine response to hypoglycaemia was attenuated by lactate (P < 0.05 for adrenaline and noradrenaline). 4. Thus intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin-dependent diabetes.

Adult↗
PubMed1998

Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

3-Hydroxybutyric Acid↗
PubMed1997

William Heberden revisited: postprandial angina-interval between food and exercise and meal composition are important determinants of time to onset of ischemia and maximal exercise tolerance.

OBJECTIVES: This study aimed to explore the hemodynamic responses to ingestion of meals of different composition in patients with chronic stable angina and to assess the effect of these meals on time to onset of > 1-mm ST segment depression and limiting angina pectoris during exercise. BACKGROUND: To our knowledge, no study has assessed the effect of meal composition and timing of exercise in patients with coronary artery disease. METHODS: Fifteen patients with chronic stable angina visited our laboratory in the fasted state on three occasions. Measurements of cardiac output, heart rate and blood pressure were taken while patients were standing. A modified Bruce exercise test was then carried out, during which time to onset of > 1-mm ST segment depression and limiting chest pain were recorded. Patients then ate a 2.5-MJ high fat or high carbohydrate meal; on the third occasion, no meal was taken. At 30 min and 1 h after eating the meals, rest hemodynamic measurements and exercise tests were repeated. RESULTS: The high fat meal did not affect exercise variables, whereas the high carbohydrate meal resulted in a reduction in time to onset of ST segment depression of 74.4 +/- 22.2 s (mean +/- SEM) during exercise at 30 min (p < 0.01), and at both 30 and 60 min after the high carbohydrate meal, limiting chest pain occurred 50 to 90 s earlier than when patients fasted (p < 0.01). CONCLUSIONS: One hour after a high carbohydrate meal, the onset of angina during exercise occurs earlier than in the fasted state. Despite similar hemodynamic adjustments, a high fat meal does not affect exercise time.

Aged↗
PubMed1997

Thoracic epidural analgesia started after cardiopulmonary bypass. Adrenergic, cardiovascular and respiratory sequelae.

The effects of thoracic epidural analgesia started after cardiopulmonary bypass were studied on the subsequent adrenergic, cardiovascular and respiratory responses. Sixteen cardiac surgical patients received either a standardised general anaesthetic (control group) or a standardised general anaesthetic and thoracic epidural analgesia (epidural group). The epidural catheter was sited before surgery and heparinisation. Following discontinuation of cardiopulmonary bypass, patients in the epidural group were given 15 ml bupivacaine 0.5% down the catheter followed by an infusion of bupivacaine 0.375% at 5-8 ml.h-1 after surgery. The control group received an intravenous morphine infusion on completion of surgery. The adrenergic response was assessed by measuring arterial catecholamine concentrations. Respiratory function was determined by spirometry, peak expiratory flow and arterial partial pressure of oxygen while breathing air. Pain scores were also obtained. After cardiopulmonary bypass the increases in catecholamine concentrations were effectively inhibited in the epidural group for the remainder of the study (p < 0.05). Postoperative respiratory function was less impaired in the epidural group, with higher forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow (p < 0.05). Pain scores were also significantly lower in the epidural group (p < 0.05). There were no significant differences in cardiovascular parameters.

Aged↗
PubMed1996

Epidemiology of infection due to Escherichia coli O157: a 3-year prospective study.

A 3-year study of Escherichia coli infections in Grampian Region was conducted to ascertain the incidence, document clinical sequelae and identify at-risk groups. Approximately 30,000 stools from patients with acute diarrhoea were screened for E. coli O157, and an epidemiological questionnaire filled in for each patient whose stool was positive. Eighty-three patients were studied. The annual incidence was 6 per 100, 000. Proportionately more infections occurred in people involved in agriculture. Evidence was seen of case-to-case transmission, and contamination of a water supply. Eight cases developed haemolytic uraemic syndrome (HUS). There were 2 deaths due to HUS and 2 due to haemorrhagic colitis (HC). Symptomatic E. coli infection is relatively common in the Grampian Region, more common in the agricultural community, and is the main cause of HUS in this Region.

Adolescent↗
PubMed1996

Central and peripheral haemodynamic responses to high carbohydrate and high fat meals in human cardiac transplant recipients.

1. Patients with autonomic dysfunction and elderly people with an age-related decline in autonomic function can suffer from a fall in blood pressure after eating. While the cardiovascular changes after eating and the effect of meal composition on these changes are well established, the underlying mechanisms are less clear. 2. This study assessed the cardiac, circulatory and humoral responses to ingestion of isoenergetic (2.5 MJ) high carbohydrate and high fat meals in nine orthotopic cardiac transplant recipients, who before transplantation had significant circulatory, metabolic and autonomic abnormalities and after transplantation had complete or partial extrinsic cardiac denervation, and compared them to the responses seen in nine healthy age-matched control subjects. 3. All variables were measured non-invasively. Cardiac transplant recipients, despite cardiac denervation, showed a normal heart rate response to high carbohydrate and high fat meals (maximal increase at 30 min postprandially + 7.8 +/- 1.1 and + 63 +/- 1.4 beats/min respectively), a normal cardiac output response to the high carbohydrate meal (maximal increase at 30 min + 1.16 +/- 0.25 l/min), but a significantly attenuated cardiac output response to the high fat meal. Cardiac transplant recipients had attenuated superior mesenteric artery blood flow responses after both meals (P < 0.05) and an attenuated calf vascular resistance response after the high fat meal (P < 0.01). Throughout the study after both meals, cardiac transplant recipients maintained blood pressure. 4. This study demonstrates that cardiac transplant recipients, despite partial or complete cardiac denervation, have a normal chronotropic response to food and a normal cardiac output response to a high carbohydrate meal. The attenuated cardiac output response to a high fat meal did not compromise blood pressure, due at least in part to decreased splanchnic vasodilatation.

Adult↗
PubMed1996

Metabolic responses of canine gracilis muscle during contraction with partial ischemia.

The metabolic effects of partial ischemia on canine skeletal muscle were examined during 20 min of isometric contraction. A reduction in blood flow of approximately 75% resulted in an approximate 40% reduction in contractile function. Muscle lactate accumulation and phosphocreatine (PCr) hydrolysis were greater during ischemia, indicating a greater reliance on anaerobic ATP regeneration. Pyruvate dehydrogenase transformation to its active form (PDCa) during contraction was not affected by ischemia, such that PDCa did not appear to be a determinant of skeletal muscle fatigue. Acetylcarnitine concentration was greater during ischemic contraction and inversely correlated with PCr concentration (r = -0.79, P<0.01). Furthermore, acetylcarnitine accumulation and PCr degradation correlated with the degree of skeletal muscle fatigue (r = 0.56, P<0.05 and r = 0.70, P<0.01, respectively). Thus the greater the acetyl group oxidation, the lesser the contribution from anaerobic ATP provision and, subsequently, the smaller the degree of muscle fatigue observed. The metabolic characteristics of this model of ischemic muscle contraction are indistinguishable from the normal metabolic responses observed with increasing contractile intensity.

Acetylcarnitine↗
PubMed1995

Septic patients in multiple organ failure can oxidize infused glucose, but non-oxidative disposal (storage) is impaired.

1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure. 2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent D-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects. 4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P < 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P < 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P < 0.01) over the course of the clamp and was significantly lower than in the control subjects (P < 0.01). 5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects. 6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.

Adolescent↗
PubMed1995

Post-surgery epidural blockade with local anaesthetics attenuates the catecholamine and thermogenic response to perioperative hypothermia.

Core (aural canal) and mean skin (15 sites) temperatures, plasma adrenaline, noradrenaline and metabolites, and gaseous exchange were measured before, during and for 4 h after surgery in sixteen patients scheduled for elective colorectal surgery. All patients received general anaesthesia and no measures were taken to prevent the perioperative loss of body heat. At time of abdominal wall closure, when the core temperature was below 35.0 degrees C, the patients were randomly allocated to receive either 20-30 mg of papaveretum i.v. (papaveretum group, n = 8) or 15 ml of bupivacaine 0.75% via thoracic (T9) epidural route to obtain a T4-S5 sensory blockade (epidural group, n = 8). Continuous infusion of either i.v. papaveretum or epidural 0.25% bupivacaine was continued after surgery. During the recovery period of four hours the rate of increase in core and mean skin temperatures was significantly slower in the epidural group compared with the papaveretum group (P < 0.01). Plasma catecholamine concentrations remained elevated after surgery in the papaveretum group, whilst they decreased significantly once epidural blockade was established (P < 0.001). There was a lower trend, however not significant, in the rise of postoperative oxygen consumption and plasma glucose concentration in the epidural group compared with the papaveretum group.

Aged↗
PubMed1995

Effect of bran particle size on gastric emptying and small bowel transit in humans: a scintigraphic study.

Bran is an effective treatment for constipation but its use is often limited by heartburn and bloating. This study examined the effect of fine and coarse bran (15 g) on the gastric emptying and small bowel transit of a 325 kcal rice test meal. Twelve healthy volunteers underwent a three way cross over study, ingesting the technetium-99m labelled rice meal with or without 15 g of indium-111m labelled fine or coarse bran, in random order. Serial scintigraphic images were obtained to define gastric emptying and colonic arrival of label. Compared with control values (99 (9) minutes) (mean (SEM)), the time to 50% gastric emptying was significantly delayed by coarse but not fine bran, being 121 (6) and 104 (9) minutes respectively, p < 0.05, n = 12. Fundal emptying was unchanged but both brans seemed to increase the proportion of isotope in the antrum at 90 minutes. Small bowel transit was slightly faster with both bran types but in this study the difference was not significant. Both the bran and rice labels moved down the gut without significant separation. Fine bran causes less disturbance of gastric physiology than coarse bran.

Adult↗