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Biomedical subjects

H G Dean

Publications and source records attributed to H G Dean.

At least 19 recordsLinked to original sources
PubMed2001

Neonatal catecholamine levels and neurodevelopmental outcome: a cohort study.

AIMS: To determine whether neonatal plasma catecholamine concentrations can be used to predict (a) death plus disability and (b) motor and cognitive impairment at 5 years of age. METHODS: A cohort comprised 136 preterm infants from two randomised controlled trials of neonatal sedation (1989-1992). Adrenaline (epinephrine) and noradrenaline (norepinephrine) were measured at baseline (first day) and 24 hours later. Intelligence and motor ability were assessed at 5-6 years. RESULTS: Infants who died or sustained disability had significantly higher plasma noradrenaline levels on the second day of life. Noradrenaline levels above 9.0 nmol/l were most predictive of death (likelihood ratio 3.27; 95% confidence interval 1.48 to 7.23) and death plus disability (likelihood ratio 3. 55; 95% confidence interval 1.77 to 7.10). There was no correlation between neonatal catecholamine levels and cognitive or motor impairment at 5-6 years. CONCLUSIONS: Elevated noradrenaline levels are associated with adverse outcome in preterm infants; however, the power to predict death or disability is limited and they are not predictive of later motor or cognitive impairment.

Biomarkers↗
PubMed1993

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Analgesia↗
PubMed1992

Effect of morphine and pancuronium on the stress response in ventilated preterm infants.

Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.

Blood Pressure↗
PubMed1991

Haemostatic responses and vasopressin release during colonoscopy in man.

1. During major abdominal surgery there are increases in Factor VIII and plasminogen activator activity, associated with elevated plasma concentrations of vasopressin, of a magnitude shown to affect haemostasis. 2. To investigate the mechanisms involved in the haemostatic response to surgery, 12 patients undergoing fibre-optic colonoscopy were studied, of which six had a complete and six had an incomplete examination. 3. Venous blood samples were taken before, during and after the procedure for assay of plasma vasopressin, adrenaline and noradrenaline concentrations, Factor VIII coagulant activity, von Willebrand factor antigen level, euglobulin clot lysis time, tissue-type plasminogen activator activity and tissue-type plasminogen activator inhibition. 4. In the six patients who underwent a complete procedure the median plasma vasopressin concentration rose from 0.6 pg/ml to 153 pg/ml during colonoscopy. Factor VII coagulant activity rose from 0.9 to 2.4 i.u./ml and von Willebrand factor antigen level rose from 139 to 224%. Plasminogen activator activity increased from 20 to 144 units and tissue-type plasminogen activator activity rose from 107 to 1338 m-i.u./ml, whereas tissue-type plasminogen activator inhibition fell from 4.8 to 1.0 i.u./ml. 5. In the six patients in whom a limited procedure was performed, there were no changes in haemostatic function or in plasma vasopressin concentration. Plasma concentrations of adrenaline and noradrenaline did not change in either group. 6. The results indicate that vasopressin regulates the intrinsic coagulation pathway and fibrinolytic system in the absence of adrenaline release.

Adult↗
PubMed1991

Platelet activation in nocturnal asthma.

Platelet activation may be a factor in the bronchial hyperresponsiveness that characterises asthma. As hyperresponsiveness is increased at night, changes in platelet activation over 24 hours were related to the diurnal changes in peak expiratory flow and plasma catecholamine concentrations in five subjects with asthma and five normal subjects. The effect of muscarinic receptor blockade with intravenous atropine at 0400 hours on these measurements was also studied. Platelet activation, assessed as the ration of beta thromboglobulin to platelet factor 4, was highest when the peak expiratory flow rate was at its lowest in the asthmatic subjects. There was no correlation between platelet activation and plasma catecholamine concentrations. Intravenous atropine did not alter the ratio of beta thromboglobulin to platelet factor 4, suggesting that parasympathetic activity is not the cause of the increased platelet activation at night.

Adult↗
PubMed1990

Adrenaline and nocturnal asthma.

OBJECTIVE: To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN: Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS: Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES: Peak expiratory flow rate and plasma adrenaline. RESULTS: Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION: A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma.

Adult↗
PubMed1990

The effect of modified electroconvulsive therapy on vasopressin release and haemostasis in man.

Plasma concentrations of plasminogen activator activity (PAA) and factor VIII are partly controlled by circulating adrenaline and vasopressin. Acute rises in PAA and factor VIII occur during electroconvulsive therapy (ECT). To investigate the relationships between vasopressin (aVP), adrenaline and changes in PAA and factor VIII during ECT, 8 female and 2 male patients, median age 57 years (range 39-75) undergoing modified ECT had venous blood samples taken before and at 2 min, 15 min, 60 min and 24 h after cessation of seizure activity. AVP rose from 0.5 before ECT to 35.5 pg/ml at 2 min (P less than 0.005) and fell thereafter. PAA (10(6)/ECLT2) increased from 22 to 69 units (P less than 0.005) over the same time and fell to 13 units at 24 h (P less than 0.02). Tissue plasminogen activator activity (tPA) rose from 162 before to 1447 mIU/ml at 2 min. (P less than 0.005) and its inhibition activity fell from 8 to 3.75 IU/ml (P less than 0.005) over the same time and rose to 10.4 IU/ml after 24 h (P less than 0.02). There were no changes in adrenaline, noradrenaline, factor VIIIc, vWF or fibrinopeptides A and B beta 15-42. AVP correlated with tPA (rs = 0.64, P = 0.0022) and PAA (rs = 0.61, P = 0.004). These results support the hypothesis that aVP has a role in the regulation of fibrinolytic activity mediated by an increase in tPA. The absence of a factor VIII response may indicate that adrenaline is more important in the regulation of factor VIIIc and vWF.

Adult↗
PubMed1989

Effects of chronic low doses of d-fenfluramine on weight gain and calorie intake, brown adipose tissue thermogenic parameters and brain neurotransmitter content in rats fed chow or palatable diets.

Male black-hooded rats of original age 3 months were maintained on either a standard laboratory chow diet or a palatable diet (32 animals in each group). After two months, when clear increases in weight gain and calorie intake in the latter group were evident, eight animals from each group were killed for analysis. For one further month, eight animals from each group received low doses (1-3 mg/kg/day) of d-fenfluramine in drinking water, another eight served as untreated controls, and the remaining eight were pair-fed to the treated groups. On killing, the interscapular brown adipose tissue (BAT) mass, and also BAT mitochondrial protein and uncoupling protein contents, and BAT mitochondrial cytochrome oxidase activity and GDP-binding were measured. Gross brain chemical changes were assessed by measuring whole brain contents of serotonin, noradrenaline and dopamine. The palatable diet produced clear increases in weight gain, calorie intake, total BAT mass, BAT mass with respect to body mass, total BAT mitochondrial protein and total amounts of uncoupling protein in each case; however, BAT mitochondrial protein per unit of BAT mass was not significantly increased, nor was the amount of uncoupling protein per mg of mitochondrial protein. Small, but variable, increases in brain neurotransmitter contents were observed. Drug-treated animals showed marked reductions in calorie intake and body weight compared to untreated controls but no significant decreases in body weight compared to pair-fed controls were evident. The pair-fed (i.e. 'slimming') groups displayed a decrease in BAT thermogenic parameters: d-fenfluramine partially prevented these decreases.

Adipose Tissue, Brown↗
PubMed1989

HPLC analysis of brain and plasma for octanoic and decanoic acids.

Two methods are described for determination of octanoic and decanoic acids in plasma and brain homogenate by "high-performance" liquid chromatography with ultraviolet detection. Analysis of the underivatized acids had a detection limit of only 50 mg/L, but formation of the p-bromophenacyl ester increased the sensitivity by 100-fold, to a detection limit of 0.5 mg/L. The latter procedure gave interassay coefficients of variation of 4.1% and 4.8% for octanoic and decanoic acids, respectively. The corresponding intra-assay values were 3.95% and 4.7% (n = 6). The derivative method, applied to samples of plasma from children receiving a medium-chain triglyceride (MCT) diet, gave values in agreement with results by gas-liquid chromatography. Results have also been obtained for samples from mice, either treated with the medium-chain triglyceride diet or given infusions of sodium octanoate.

Adolescent↗
PubMed1988

Parasympathetic nervous system in nocturnal asthma.

To investigate the effect of vagal blockade with atropine on nocturnal fall in peak expiratory flow rate 10 patients with asthma who had a diurnal variation in peak expiratory flow rate of greater than 20% were given 30 micrograms/kg of intravenous atropine or a placebo at 4 am and 4 pm. Vagal blockade caused significant bronchodilatation at 4 am and 4 pm (peak expiratory flow rate rose from 260 to 390 l/min at 4 am and 400 to 440 l/min at 4 pm) and significantly increased the pulse rate from 60 to 121 beats/minute at 4 am and from 76 to 122 beats/minute at 4 pm. Nocturnal asthma was almost totally reversed, implying that vagal mechanisms are fundamental in its pathophysiology. Other mechanisms--diurnal changes in plasma adrenaline concentration, the activity of non-adrenergic non-cholinergic nerves, and circadian rhythms of inflammatory mediator activity--may also be implicated.

Adult↗
PubMed1988

Regional variation in skin blood flow response to hypoglycaemia in type 1 (insulin-dependent) diabetic patients without complications.

Body temperature falls during hypoglycaemia, perhaps as a protective mechanism. To test the hypothesis that the skin blood flow response to hypoglycaemia is specifically designed to facilitate heat loss we studied both nutritional blood flow and arteriovenous shunting of blood in skin during prolonged, controlled hypoglycaemia in man. We studied eight otherwise healthy, male, Type 1 (insulin-dependent) diabetic patients. Under Biostator control blood glucose was clamped at 8.0 (7.9-8.9), mmol/l (median and range) for 30 min, reduced to symptomatic hypoglycaemia, 1.7 (1.0-2.6) mmol/l for 20 min then raised to 4.9 (3.3-6.7) mmol/l. Interdigital skin web blood flow (laser doppler flowmeter, nutritional flow) fell during hypoglycaemia from 3.1 (2.2-3.8) to 2.4 (1.2-2.8) volts and remained depressed. In contrast, finger blood flow (venous occlusion plethysmography, arteriovenous shunt flow) started high at 54.7 (17.4-85.6), remained high at 52.7 (38.1-81.4) during hypoglycaemia but fell sharply to 25.3 (4.2-66.2) ml.min-1.100 ml-1 when symptoms were relieved. Plasma adrenaline and vasopressin both rose during hypoglycaemia from 0.4 (0.05-0.8) to 4.5 (2.3-20.2) nmol/l and from 0.5 (0.5-3.5) to 4.4 (2.0-13.9) pg/ml, respectively, and both fell sharply thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Role of the adrenal medulla in stress-induced hyperinsulinaemia in normal mice and in mice infected with Bordetella pertussis or treated with pertussis toxin.

Intranasal infection of mice with a sublethal dose of Bordetella pertussis or the intravenous administration of purified pertussis toxin resulted in a marked increase in the serum immunoreactive insulin concentration following ether stress. This stress-induced hyperinsulinaemia was not modified significantly by blockade of alpha 2-adrenoceptors with idazoxan, beta-adrenoceptors with propranolol, autonomic ganglia with hexamethonium, opioid receptors with naloxone, muscarinic cholinoceptors with atropine or by adrenal demedullation. The effect of pertussis in promoting stress-induced hyperinsulinaemia was mimicked qualitatively by alpha 2-adrenoceptor blockade, adrenal demedullation or ganglionic blockade. However, the serum immunoreactive insulin response to ether stress was smaller in animals subjected to these procedures compared with the response seen in mice infected with B. pertussis or treated with pertussis toxin. Thus, in the mouse, acute stress produces hyperinsulinaemia under conditions in which the release of adrenal medullary catecholamines is prevented, or the inhibitory action on insulin secretion is blocked by alpha 2-adrenoceptor antagonists or by pertussis toxin.

Adrenal Medulla↗
PubMed1988

Concentrations of serotonin in plasma--a test for appendicitis?

We assessed the value of measuring serotonin (5-hydroxytryptamine) in plasma (by HPLC) in the diagnosis of acute appendicitis. Values for patients with subsequently confirmed appendicitis (11-145 nmol/L, median 70 nmol/L) significantly (P congruent to 0.005) exceeded those for patients with abdominal pain in whom appendicitis was only a possible diagnosis (2-45 nmol/L, median 20 nmol/L). The results for appendicitis patients were bimodally distributed, with low results found in patients where surgery revealed gangrenous appendicitis with little viable appendicular tissue. We conclude that measuring serotonin may be of value in confirming or excluding the diagnosis of early acute appendicitis where the physical signs are equivocal, and thus helps reduce unnecessary appendectomies. However, serotonin is of little help in diagnosing gangrenous appendicitis, where physical signs are more likely to be clearcut.

Appendectomy↗
PubMed1988

Do increased catecholamines and plasma methionine enkephalin in cirrhosis promote bleeding oesophageal varices?

Increased sympathetic tone and adrenal medullary activity in hepatic cirrhosis may promote portal hypertension. We suggest that they may be imperfect homeostatic mechanisms attempting to maintain systemic arterial pressure in response to chronic vasodilatation and that small, endogenous opioid peptides may play a part in this vasodilatation. As initial investigation of this hypothesis, we measured noradrenaline (an indicator of sympathetic tone), adrenaline and methionine enkephalin in the plasma of patients with cirrhosis with oesophageal varices which had or had not bled previously, patients with cirrhosis without varices, patients with acute liver disease and controls. In patients with cirrhosis, noradrenaline, adrenaline and methionine enkephalin were all greatest in those with oesophageal varices which had previously bled. In this group, noradrenaline correlated strongly with the widely used prognostic guide, Pugh's modification of Child's classification. In patients with acute liver disease, methionine enkephalin and adrenaline were increased six- and four-fold respectively. However, noradrenaline was normal, suggesting that increased sympathetic tone in cirrhosis may develop gradually. The use of opioid antagonists may enable determination of whether elevated plasma opioid peptides in cirrhosis stimulate the increase in sympathetic tone and plasma adrenaline, and promote bleeding oesophageal varices.

Acute Disease↗
PubMed1986

The effects of ICS 205-930, a 5-HT antagonist, on arrhythmias and catecholamine release during canine myocardial ischaemia and reperfusion.

The effects of ICS 205-930 [3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester), an antagonist of 5-HT at neuronal M receptors, were examined in anaesthetised greyhounds subject to acute coronary artery occlusion and reperfusion. Intravenous administration of 0.3 or 2.0 mg kg-1 of ICS 205-930 did not significantly alter haemodynamics or blood gases. The higher dose had marked antiarrhythmic activity. The total number of ischaemia-induced extrasystoles was reduced to 167 +/- 64 compared with 467 +/- 99 in controls. Ventricular fibrillation induced by reperfusion after 40 min of ischaemia was also significantly reduced from 80 to 33%. Immediately following release of the coronary artery occlusion significant increases in plasma noradrenaline and dopamine concentrations were detected in local coronary venous blood draining from the ischaemic area in control dogs. This catecholamine release was also evident in the dogs which received 2 mg kg-1 ICS 205-930 but was less marked. Thus the antiarrhythmic activity of ICS 205-930 may be related to antagonism of detrimental effects of 5-HT, such as the ability to facilitate the release of noradrenaline from sympathetic nerve terminals in the heart, although other mechanisms may be involved.

Animals↗
PubMed1986

Vasopressin and catecholamine secretion during apomorphine-induced nausea mediate acute changes in haemostatic function in man.

Seven male volunteers were given apomorphine (14-20 micrograms/kg) subcutaneously on a total of ten occasions. Nausea was experienced on six occasions and on four occasions there was no effect. Venous samples were taken before injection, at peak nausea and 20 min later for assay of factor VIII coagulant activity (FVIIIC), von Willebrand factor antigen (vWFAg), the ristocetin cofactor (FVIIIRiCof), euglobulin clot lysis time (ECLT), fibrinopeptide A (FPA), FPA generation time, activated partial thromboplastin time (APTT), vasopressin (aVP) and adrenaline. During nausea plasma aVP concentrations rose from median values of 0.4 pg/ml (at time 0) to 76 pg/ml at peak nausea and fell to 32 pg/ml 20 min later. Adrenaline rose from 0.36 to 0.91 nmol/l (P less than 0.05) before falling to 0.55 nmol/l. During nausea, FVIIIC rose from 100% to 143% (P less than 0.05) and to 214% (P less than 0.05) 20 min later. FVIIIRiCof and vWFAg showed similar changes. Plasminogen activator activity (10(6)/ECLT2) rose from 23 units at time 0 to 592 units during nausea and 1135 units (P less than 0.05) after 20 min. The APTT fell from 49 s to 44 s during the study, plasma FPA levels and the FPA generation time both remained unchanged. On the four occasions nausea was not experienced, there were no changes in vasopressin and catecholamine concentrations nor in haemostatic function. During the study, plasma aVP concentrations rose to levels previously shown to influence haemostatic function. This provides further support for the view that aVP has a secondary role as a mediator of acute changes in haemostasis, and during nausea contributes with adrenaline to an abrupt change in factor VIII and fibrinolytic activator activity.

Apomorphine↗
PubMed1986

Effect of acute renal failure on the disposition and elimination of [3H]N-acetyl procainamide ethobromide in the rat.

The effect of glycerol-induced acute renal failure (ARF) on the disposition and elimination of the organic cation [3H]N-acetyl procainamide ethobromide (APAEB) was investigated in the rat. In rats with ARF the plasma clearance, rate constant for the terminal portion of the plasma concentration-time curve and apparent volume of distribution were all decreased (P less than 0.01). Furthermore, the renal clearance of APAEB and the percentage dose excreted in urine were reduced by 85 and 74%, respectively. Decreased renal excretion probably accounted for the altered kinetics of APAEB in ARF because ligation of the renal pedicles of control rats produced changes in the kinetics of APAEB that were similar to those seen in animals with ARF. No change in either the hepatic content of APAEB or its biliary excretion were detected in rats with ARF. Similarly, the hepatic handling of ouabain and taurocholic acid was previously found to be unaltered in ARF; but by contrast, the hepatic uptake and initial biliary excretion of bromosulphophthalein and indocyanine green were decreased (Bowmer & Yates 1984, Br. J. Pharmacol. 83: 773-782). Together these studies indicate that there is a selective impairment of hepato-biliary transport in ARF.

Acecainide↗