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Biomedical subjects

N Dalton

Publications and source records attributed to N Dalton.

At least 37 records · Page 2Linked to original sources

Hormonal response to blood volume expansion in diabetic subjects with and without autonomic neuropathy.

The hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin-dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age-and-sex-matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P less than 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P less than 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.

Adult↗

Evaluation of Björk-Shiley prosthetic valves by real-time two-dimensional Doppler echocardiographic flow mapping.

We studied the value of two-dimensional Doppler echocardiographic color flow mapping for identifying normal transvalve flow profiles and valve malfunction in 20 patients with Björk-Shiley prosthetic valves. Seven patients had Björk-Shiley prosthetic valves in the aortic position alone, seven in the mitral position, and six had prosthetic valves in both the aortic and mitral positions. In 10 patients with normally functioning mitral valves, the ratios of the maximal major and minor Doppler-imaged orifice flow diameters to the valve ring diameters were 25 +/- 3% (mean +/- SD) and 24 +/- 3%, respectively, similar to values reported in in vitro studies. No mitral regurgitation was found in these patients by two-dimensional Doppler echocardiographic flow mapping or by spectral Doppler. Of the 10 clinically normal aortic Björk-Shiley valves, no valvular regurgitation was found by color flow mapping, whereas mild aortic regurgitation was found in two patients with the use of spectral Doppler. Malfunction of six valves was documented in five patients and was confirmed by cardiac catheterization and/or surgery. These included one case of focal fibrous ingrowth involving primarily the minor orifice of a mitral prosthetic valve, one case of mitral valve prosthetic thrombosis with decreased major and minor orifice flow diameters and valvular regurgitation, and four cases of paravalvular regurgitation involving prosthetic valves in the aortic position (three patients) and the mitral position (one patient). Two-dimensional Doppler echocardiographic flow mapping provides new observations that may aid in identifying Björk-Shiley prosthetic valve malfunction. By localizing precisely the site of prosthetic stenosis or regurgitation, it may also assist in defining the cause of valve malfunction.

Adolescent↗

Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma.

Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV1 were 21.9 +/- 2.3% (mean +/- SEM; n = 8) and 5.5 +/- 1.3% (mean +/- SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time-dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise-induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release.

Adult↗

A comparison of mediator and catecholamine release between exercise- and hypertonic saline-induced asthma.

Serum neutrophil chemotactic activity (NCA) and plasma histamine concentrations were measured in 9 asthmatic subjects with exercise-induced asthma after inhalation challenge with ultrasonically nebulized 3.6% hypertonic saline, which was administered either in a dose-dependent manner (HSDR) or as a continuous single dose (HSC), and after cycle ergometer exercise. The mean decreases in FEV1 elicited by HSDR, HSC, and exercise were 26, 27, and 25%, respectively, and were not significantly different. There was an approximate 300% maximal increase in NCA detected after both HSC and exercise challenges. Gel filtration chromatography on columns of Ultragel ACA 34 indicated that the NCA released after HSC provocation and exercise were 600 to 700 kDa. There was an approximate 100% maximal increase in NCA after HSDR challenge, and this was significantly less (p = 0.016) than that after HSC and exercise. Exercise but not hypertonic challenge was associated with a basophilia and a significant increase in plasma histamine. There was a significant increase in plasma norepinephrine concentrations after exercise but not after HSC challenge in 7 asthmatics. Epinephrine concentrations did not change after exercise or HSC inhalation. NCA was measured in 5 subjects subjected to 2 HSC challenges that were separated by 60 min. There was an increase in NCA detected after both provocations. The increase after the second challenge was significantly greater (p = 0.27 x 10(-4)) than that observed after the initial provocation, despite a substantially reduced bronchoconstrictor response after the second challenge.

Adolescent↗

Phaeochromocytoma: report of three cases.

The diagnosis and investigation of phaeochromocytoma was reviewed in three patients presenting to the paediatric renal centre with malignant hypertension. The initial diagnosis was made using urinary 4-hydroxy-3-methoxymandelic acid (VMA) and plasma adrenaline and non-adrenaline estimations. Our experience of the localization of phaeochromocytoma with ultrasound, 131I-meta-iodobenzylguanidine (MIBG) and venous sampling was discussed and we have reappraised our approach to the localization of these tumours.

Adrenal Gland Neoplasms↗

Investigation of adrenomedullary function in atopic dermatitis.

Adrenomedullary function in patients with atopic dermatitis was assessed by measurement of plasma levels of catecholamines (adrenalin and noradrenalin) and cyclic AMP in response to the stimuli of standing after lying supine, and a 5-min infusion of histamine in the standing position (i.e. histamine plus standing). Plasma clearance of adrenalin was examined by measurement of plasma catecholamine and cyclic AMP levels following a 15-min intravenous infusion of adrenalin in the supine position. Resting plasma levels of adrenalin, cyclic AMP and noradrenalin were not statistically different in atopic patients and normal controls. Standing or intravenous infusion of histamine in the standing position caused a rise in plasma catecholamine levels. Plasma adrenalin, cyclic AMP and noradrenalin levels in response to these stimuli and the rate of clearance of exogenous adrenalin from the plasma were not significantly different in patients with atopic dermatitis and in normal subjects.

Adolescent↗

Hyponatraemia in premature babies and following surgery in older children.

Hyponatraemia implies water retention in excess of sodium with or without increased loss of sodium from the body; extracellular fluid volume may be increased, normal or reduced. It has many causes which are briefly reviewed. Among these is the rare syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is suggested that SIADH is often diagnosed incorrectly because the raised ADH levels are appropriate for the volume status of the child. Precision in the diagnosis is important because whilst water restriction is necessary for the treatment of SIADH, other measures including the administration of extra fluid are often required if the raised ADH is appropriate. Hyponatraemia in the newborn may be caused by prerenal failure, renal failure or renal sodium wasting which is common in premature infants. Careful control of sodium intake as well as water intake is vital in this age group. Surgery is associated with water retention, but recent studies suggest that ADH levels are raised post-operatively because of volume depletion and that present recommendations for fluid therapy during and following surgery are inadequate. The use of electrolyte-free dextrose solutions should be abandoned and more liberal use of physiological saline or colloid is recommended.

Adolescent↗

Systemic absorption of inhaled epinephrine.

To determine the systemic absorption of epinephrine when it is given by inhalation, six normal volunteers were given 15 puffs, followed by 30 puffs, of epinephrine from a pressurized aerosol (160 micrograms epinephrine/puff). The peak mean (+/- SE) plasma epinephrine levels were 1.50 (+/- 0.61) and 4.22 (+/- 1.93) nmol/L 1 minute after each dose, respectively. The effect on physiologic finger tremor correlated with the plasma epinephrine level and returned to baseline 20 minutes after taking the higher dose. There was a small fall in mean plasma potassium levels of 0.45 mmol/L and a small rise in plasma glucose levels of 0.81 mmol/L. On a separate occasion an injection of 0.3 ml of 1/1000 (300 micrograms) epinephrine was given subcutaneously to the same individuals. This caused a peak plasma epinephrine level of 2.43 (+/- 0.47) nmol/L at 10 minutes, and this was still raised at 2.05 (+/- 0.41) nmol/L after 40 minutes. The maximum fall in the mean plasma potassium level was 0.43 mmol/L after the injection.

Absorption↗

Plasma catecholamine levels during water immersion in man.

In ten normal subjects thermoneutral neck-out water immersion produced a highly significant natriuresis and diuresis mediated via an induced central hypervolaemia. During immersion suppression of plasma noradrenaline and adrenaline was observed but no change occurred in plasma dopamine levels. No correlation was found between the suppression of noradrenaline and the diuresis and natriuresis. The reduction in plasma noradrenaline observed may reflect a widespread diminution of sympatho-adrenal activity during water immersion. This reduction could be a consequence of the cardiovascular changes of immersion and may not be directly involved in the mechanism of the renal response.

Adult↗

The purification and characterisation of hyaluronidase from the venom of the honey bee, Apis mellifera.

Hyaluronidase has been purified from the venom of the honey bee, Apis mellifera. The purification proved remarkably difficult, requiring a large number of chromatographic steps culminating in the removal of traces of phospholipase A2 with an affinity purified rabbit anti-phospholipase A2 immunosorbent column. The purified enzyme showed a 1143-fold increase in specific activity and was homogeneous. Electrophoresis in polyacrylamide gels (12%) containing sodium dodecyl sulphate (pH 8.9) or urea (pH 2.8) and electrofocusing in polyacrylamide (5%) gave a single band. The final product contained less than 0.1% phospholipase A2 and less than 1.5% acid phosphatase and gave a single line of precipitation against rabbit anti-hyaluronidase but was not precipitated by rabbit anti-phospholipase A2. Previous reports of instability were not confirmed, and we found the enzyme to be highly stable over a wide range of temperature and pH, and to denaturing agents. Purified hyaluronidase was found to be 'sticky' when highly pure and at low concentration, and adhered strongly to Sephadex G-75. The relative molecular mass was estimated at 35 000-37 000 by gel filtration, and at 41 000 by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. A value of 50 000 was obtained by ultracentrifugation assuming a partial specific volume of 0.73 cm3/g. Hyaluronidase was found to be a minor allergen in bee venom allergic patients.

Amino Acids↗

Protective effect of circulating epinephrine within the physiologic range on the airway response to inhaled histamine in nonasthmatic subjects.

The specific airway conductance response of six normal subjects to increasing doses of inhaled histamine was studied on two occasions. On each occasion either epinephrine (0.025 micrograms/kg/min) or saline was infused intravenously during the histamine challenge. This dose of epinephrine, when it was administered to seated normal subjects, produces plasma levels similar to those found at the end of strenuous exercise. Epinephrine caused a significant elevation in the concentration of histamine required to cause a 35% fall in specific airway conductance (PC35), although this was in part caused by a small airway dilator effect. The mean (+/-SD) PC35 rose from 21 mg/ml (+/-6) during saline infusion to 58 mg/ml (+/-27) during epinephrine infusion, p less than 0.05. Levels of circulating epinephrine, similar to those found during exercise in normal subjects, appear to be capable of protecting against bronchoconstrictor stimuli.

Administration, Intranasal↗

Adrenaline secretion during exercise.

By studying six normal subjects during graduated treadmill exercise, we have confirmed that there is very little rise in venous plasma adrenaline levels during mild or moderate exercise. During a second study, adrenaline was infused intravenously in six resting subjects at a rate of 0.025 micrograms min-1 kg-1. This elevated the basal plasma adrenaline level from 0.28 +/- 0.04 nmol/l to 0.92 +/- 0.16, 1.16 +/- 0.20 and 1.28 +/- 0.19 nmol/l at 3, 5 and 7 min after the start of the infusion. The same adrenaline infusion was repeated in the same subjects 7 min after they started moderate exercise at a constant rate on a static exercise bicycle. Just before the start of the infusion, 7 min after the onset of exercise, plasma adrenaline had risen to 0.36 +/- 0.07 nmol/l. This rose to 1.86 +/- 0.30, 1.98 +/- 0.26 and 2.19 +/- 0.29 nmol/l at 3, 5 and 7 min after the start of this second infusion. Five minutes after the end of the infusion, while the subjects were still exercising, the mean level was 0.56 +/- 0.04 nmol/l. The venous plasma level of adrenaline is the result of a balance between the secretion of adrenaline by the adrenal medulla and the clearance of adrenaline from plasma. Our results suggest that the lack of any significant rise in plasma adrenaline during moderate exercise does not result from an accelerated clearance of adrenaline by exercising tissue. The clearance rate of adrenaline from plasma is reduced during exercise. There is no significant increase in secretion by the adrenal medulla in response to the stimulus of mild or moderate exercise.

Adult↗

Metabolic effects of physical exercise in insulin-dependent diabetics controlled by continuous subcutaneous insulin infusion or conventional injection therapy.

The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion. Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P less than 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.

Adult↗

Oral essential aminoacid and ketoacid supplements in children with chronic renal failure.

The effects on growth, body composition, and metabolism of a protein-restricted diet supplemented with essential aminoacids, the calcium-ketoacids of valine, leucine, isoleucine, and phenylalanine, and the calcium-hydroxyacid of methionine, were investigated in seven growth-retarded children with chronic renal failure. During 0.4 to 1.0 years of treatment there were significant increases in growth velocity and upper arm circumference SD scores, body cell mass (intracellular water calculated as tritium space minus corrected sodium bromide space) and serum transferrin. Blood urea and urea:creatinine ratio fell in all children. Renal function assessed from plasma creatinine and 51Cr EDTA clearance did not change significantly. During treatment there was an increase in plasma calcium, high levels necessitating brief interruption of therapy in two children, and a decrease in plasma phosphate. Levels of serum parathormone fell in all children, and were correlated inversely with plasma calcium and positively with plasma phosphate. Abnormalities compared to control children in blood aminoacid and branched-chain ketoacid levels were unaffected by treatment. These results suggest that a protein-restricted diet supplemented with essential aminoacids and calcium-keto and hydroxyacids may be useful to improve linear growth and nutritional status in children with chronic renal failure, and that a reduction in hyperparathyroidism may be partly responsible for some of the beneficial effects observed.

Amino Acids, Essential↗

A comparison of the bronchodilator and vasopressor effects of exercise levels of adrenaline in man.

1. Plasma adrenaline was measured at rest and on exercise in six normal, non-atopic subjects. The exercise test produced a minimum tachycardia of 158 beats/min and a mean plasma adrenaline level of 1.89 nmol/l. 2. On a separate occasion, two doses of L-adrenaline (0.025 micrograms min-1 kg-1 and 0.05 micrograms min-1 kg-1) were infused in the same subjects at rest to produce two mean plasma levels similar to those found on exercise. 3. Significant bronchodilation and elevation of plasma glucose occurred with both infusion doses when compared with placebo. 4. Neither infusion caused a significant change in heart rate and only the higher dose caused a small but significant rise in systolic and fall in diastolic blood pressure. 5. Our results suggest that adrenaline as a hormone, at the levels found on exercise, is capable of causing bronchodilation and glycogenolysis in normal subjects. Its contribution to the cardiovascular response to exercise appears to be slight and suggests that its role in cardiovascular physiology may also be marginal.

Adult↗

Effect of a 2 week course of oral salbutamol on adrenomedullary function in normal subjects.

1 The adrenal medullary response to intravenous histamine infusions (0.1 and 0.4 micrograms kg-1 min-1 histamine base) was studied in six normal subjects. 2 After a 2 week course of oral salbutamol (8 mg slow release twice daily) plasma adrenaline levels, thought to reflect adrenomedullary function, were unchanged both at rest and in response to histamine infusion. 3 The present study does not support our original hypothesis that salbutamol may be capable of suppressing the adrenal medulla in normal subjects.

Administration, Oral↗

The effect of posture on the sympathoadrenal response to theophylline infusion.

We studied the effect of posture on the sympathoadrenal response to intravenous theophylline in six normal subjects. On three separate occasions they received an intravenous infusion of either theophylline (6 mg/kg) while supine, theophylline (6 mg/kg) while standing or saline as placebo while standing. With the subjects standing theophylline caused tremor, a peak heart rate of 99 +/- 6 beats/min, and an elevation of plasma cyclic AMP from 9.3 +/- 0.7 to 15.1 +/- 1.7 nmol/1 (mean +/- s.e. mean). There was a small, but significant, elevation of plasma adrenaline, noradrenaline and glucose. The elevation in plasma catecholamines was insufficient to explain either the sympathomimetic effects of theophylline or the rise in plasma cyclic AMP. Theophylline had little or no effect with the subjects supine. The mean peak theophylline concentration following infusion was significantly higher with the subjects upright than when supine (18.3 c.f. 12.4 mg/l, P less than 0.025). However, adequate plasma levels of theophylline were obtained in all subjects when lying or supine. Analysis of individual data suggests that differences in plasma levels of theophylline are unlikely to account for the increased effects seen on standing. The mechanism of action of theophylline cannot be explained by increased secretion of catecholamines alone. Theophylline appears to amplify the increased sympathetic activity associated with standing and this is probably by phosphodiesterase inhibition.

Adrenal Glands↗