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Biomedical subjects

A D Struthers

Publications and source records attributed to A D Struthers.

At least 217 records · Page 12Linked to original sources
PubMed1991

Atrial natriuretic factor inhibits metoclopramide stimulated aldosterone release in man.

1. Atrial natriuretic factor (ANF) has an inhibitory effect on angiotensin II and ACTH stimulated aldosterone secretion in man. The selectivity of this aldosterone suppressing effect of ANF is unclear in man. The present study investigated the effect of ANF on the increase in plasma aldosterone due to metoclopramide in man. 2. Eight normal male volunteers were studied on three occasions. Metoclopramide (10 mg slow i.v.) was given on all study days and each volunteer was randomised to receive 45 min infusion of either 5% D-glucose (placebo) or ANF (99-126) 3 or 15 pmol kg-1 min-1. 3. Metoclopramide increased plasma aldosterone to approximately 170% of baseline levels (P less than 0.01). Concomitant infusion of ANF 3 pmol kg-1 min-1 and 15 pmol kg-1 min-1 significantly attenuated this rise in plasma aldosterone to approximately 130% (P less than 0.05) and 110% (P less than 0.01) of baseline values respectively. 4. It is suggested, in the light of previous findings, that the inhibitory effect of ANF represents a non-selective action of ANF on aldosterone release.

Adult↗
PubMed1991

Comparison of the effects of ANF 99-126 and ANF 103-126 on captopril-induced renin release in man.

OBJECTIVE: The aim was to examine the effects of atrial natriuretic factor (ANF) 99-126 and ANF 103-126, an N-terminal shortened analogue of the peptide, on the plasma renin activity response to captopril, an inhibitor of angiotensin-converting enzyme. DESIGN: Two protocols were performed. In the first protocol, subjects were studied on three occasions. Captopril 25 mg was given and a 60 minute infusion of 5% D-glucose (placebo), or ANF 99-126 3 or 10 pmol/kg/min, was administered in a single blind randomized manner. The second protocol was divided in two parallel phases comparing ANF 103-126 either 3 or 10 pmol/kg/min to placebo. SUBJECTS: Thirty-three salt-replete healthy male volunteers aged 21-39 years were studied in the supine position. MEASUREMENTS: Plasma renin activity, plasma ANF 99-126 and ANF 103-126 levels, heart rate and blood pressure were measured. RESULTS: Compared to placebo infusion, the rise in plasma renin activity after captopril was attenuated by ANF 99-126 infusion (from 755% of baseline to 294% by ANF 99-126 3 pmol/kg/min and from 755 to 202% by 10 pmol/kg/min; P less than 0.03 and P less than 0.01 respectively). The comparable findings with ANF 103-126 were 492 to 218% (3 pmol/kg/min) and 645 to 364% (10 pmol/kg/min) (P less than 0.01 and P less than 0.01 respectively). CONCLUSIONS: The results, taken in conjunction with previous findings, suggest that atrial natriuretic factor inhibits in a non-selective manner the renin response to all secretagogues so far tested in man. The current results also suggest that the anti-renin action of atrial natriuretic factor does not depend on the first four N-terminal amino acids of the native peptide.

Adult↗
PubMed1991

Self-assessment of medical knowledge: do physicians overestimate or underestimate?

The relationship between doctors' medical knowledge and their inability to assess correctly what they know was investigated. Sixty out of 65 hospital physicians sat a MRCP Part 1 multiple-choice examination. In addition to the factual questions, they had to estimate how certain they were that their answers were correct. We confirmed that factual knowledge increased with clinical experience from the grade of house officer through to that of senior registrar. The self-assessment of likelihood of being correct revealed that, on average, doctors underestimated their knowledge by 8%. However, those who had passed their MRCP examination within the past three years over-estimated on average by 6%. We suggest that this inadequacy of self-assessment could have serious clinical implications, and should be assessed.

Educational Status↗
PubMed1990

Effect of atrial natriuretic factor on platelet function in whole blood ex-vivo in man.

Atrial natriuretic factor (ANF) binding sites have been shown to be present on human platelet membranes. We investigated the effect of an infusion of ANF 5 pmol.kg-1.min-1 on platelet aggregation in whole blood ex-vivo in 8 normal volunteers. Spontaneous platelet aggregation, collagen (0.6-2 micrograms.m.-1)-induced or ADP (0.5-2.0 microM)-induced aggregation was not affected by ANF. Plasma aldosterone was however significantly attenuated by ANF. These results show that a pharmacological dose of ANF does not affect platelet aggregation in man. These results suggest that the high plasma levels of ANF normally achieved in chronic heart failure or acute myocardial infarction are unlikely to contribute to the platelet hyperractivity, often observed in these conditions.

Adenosine Diphosphate↗
PubMed1990

Neuroendocrine changes post myocardial infarction: effects of xamoterol.

This study reports the effects of the new beta 1 adrenoceptor partial agonist, xamoterol, on neuroendocrine activity after acute myocardial infarction (AMI). Fifty-one consecutive patients with AMI were randomized to treatment with xamoterol, 200 mg twice a day, or placebo; patients were also stratified as to whether or not diuretic therapy was given for left ventricular dysfunction. Noradrenaline, plasma renin activity (PRA), and atrial natriuretic factor (ANF) were measured over a 10-day period. Noradrenaline concentrations are higher (p less than 0.05) in patients treated with diuretics at the time of admission and fell over the subsequent 10 days (p less than 0.01). Treatment with xamoterol did not affect this noradrenaline response to myocardial infarction. PRA was also significantly higher in the patients treated with diuretics, and there was a nonsignificant trend for xamoterol to blunt the PRA response in these patients. There was no difference in ANF levels between those patients who were treated with diuretics and those who were not; xamoterol did not affect ANF. Thus xamoterol does not further elevate noradrenaline levels as do conventional beta blockers, and it does not activate the renin-angiotensin system as do potent nonselective beta agonists. Furthermore, xamoterol does not increase ANF levels, probably because it is not negatively inotropic. We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure.

Adrenergic beta-Agonists↗
PubMed1990

Electrocardiographic changes induced by inhaled salbutamol after treatment with bendrofluazide: effects of replacement therapy with potassium, magnesium and triamterene.

1. Twelve normal subjects were given 5 days' treatment with (a) placebo; (b) 5 mg of bendrofluazide; (c) 5 mg of bendrofluazide plus 24 mmol of potassium; (d) 5 mg of bendrofluazide plus 24 mmol of magnesium; (e) 5 mg of bendrofluazide plus 24 mmol of potassium plus 24 mmol of magnesium; (f) 5 mg of bendrofluazide plus 50 mg of triamterene. 2. After each treatment period, subjects were given two doses of inhaled salbutamol (each of 1 mg), and measurements were made 25 min after each dose. 3. Treatment with bendrofluazide plus salbutamol produced a lower absolute level of plasma potassium than salbutamol alone, although the addition of potassium, magnesium or triamterene did not attenuate this effect. Plasma magnesium was unchanged by salbutamol. 4. Salbutamol was associated with significant electrocardiographic effects, including T-wave flattening, Q-Tc interval prolongation and, in some subjects, U-waves and S-T segment depression. 5. Prior treatment with bendrofluazide potentiated the electrocardiographic effects of salbutamol. Supplementation with potassium and magnesium had no effect on electrocardiographic changes, and the addition of triamterene to bendrofluazide only attenuated electrocardiographic responses in some subjects.

Adult↗
PubMed1990

Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene.

Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs.

Adult↗
PubMed1990

Physicians' attitudes to the treatment of elevated serum cholesterol.

A questionnaire was sent to 457 physicians (328 general practitioners, 129 hospital doctors) to assess their attitudes to and their knowledge and practice of the management of raised serum cholesterol. Replies were returned by 206 (63%) general practitioners and 95 (74%) hospital doctors. While smoking, hypertension, diabetes mellitus and elevated total serum cholesterol were recognised as major risk factors for coronary heart disease, a significant number of respondents considered serum triglycerides to be less important. Both groups of physicians start dietary management at similar total serum cholesterol levels, but hospital doctors were more likely to use dietetic services. The two groups had a similar threshold for the addition of drug therapy. A bile acid sequestrant was the favoured first choice as a cholesterol lowering agent, although a wide variety of other drugs were also chosen. The screening of high risk patients was preferred to whole population and opportunistic screening for identifying hypercholesterolaemic individuals. The findings have important implications in the delivery of services to hypercholesterolaemic patients.

Anticholesteremic Agents↗
PubMed1989

Pharmacokinetics, efficacy and adverse effects of sublingual salbutamol in patients with asthma.

Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 micrograms (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggest that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.

Administration, Inhalation↗
PubMed1989

Prior treatment with diuretic augments the hypokalemic and electrocardiographic effects of inhaled albuterol.

PURPOSE: High doses of inhaled albuterol produce substantial improvements in bronchodilatation but are associated with dose-related systemic side effects including hypokalemia and hypomagnesemia. Concomitant diuretic therapy also produces these metabolic sequelae and may therefore precipitate cardiac arrhythmias in patients taking this combination of drugs. The purpose of this study was to investigate the electrocardiographic (ECG) effects of high-dose inhaled albuterol, and to evaluate whether potentiation occurs with bendrofluazide. PATIENTS AND METHODS: Ten normal subjects (mean age [+/- SEM]: 29 +/- 2 years, four women, six men) received seven days of treatment with either bendrofluazide 5 mg or identical placebo in a single-blind, randomized, cross-over design, with a 10-day washout period. After each treatment period, responses (potassium, magnesium, ECG) to cumulative doubling doses of inhaled albuterol (100 micrograms to 2,000 micrograms) were measured. RESULTS: Baseline potassium levels (mean and 95% confidence intervals) were lower after pretreatment with bendrofluazide compared with placebo (3.07 mmol/L [2.89 to 3.25 mmol/L] versus 3.78 mmol/L [3.62 to 3.93 mmol/L]; p less than 0.001). The combination of bendrofluazide and albuterol produced a lower absolute level of potassium than did placebo and albuterol: (2.72 mmol/L [2.50 to 2.95 mmol/L] versus 3.18 mmol/L [3.09 to 3.27 mmol/L]; p less than 0.001). Mean (+/- SEM) potassium fell to a lower level with bendrofluazide and albuterol in women than in men (2.45 +/- 0.04 mmol/L versus 2.90 +/- 0.13 mmol/L; p less than 0.005). Albuterol alone produced a small but significant fall in magnesium (0.842 mmol/L [0.815 to 0.869 mmol/L] to 0.789 mmol/L [0.757 to 0.820 mmol/L]; p less than 0.001), but no further change after bendrofluazide. Pretreatment with bendrofluazide increased the frequency (p less than 0.001) and amplitude (p less than 0.05) of U waves due to albuterol. Albuterol also attenuated T-wave amplitude (p less than 0.001) and prolonged the Q-Tc interval (p less than 0.001), with no additive effect from bendrofluazide. ST-segment depression (p less than 0.001) occurred in five subjects who inhaled albuterol. CONCLUSION: These findings show that treatment with bendrofluazide augments the hypokalemic and ECG effects of high-dose inhaled albuterol. The arrhythmogenic potential of this interaction may be important in patients with acute exacerbations of chronic airflow obstruction, who have concomitant hypoxemia and ischemic heart disease.

Administration, Inhalation↗
PubMed1989

Mechanisms of the antinatriuretic action of physiological doses of angiotensin II in man.

1. Angiotensin II (ANG II; 1 ng min-1 kg-1) or 5% (w/v) D-glucose (placebo) was infused in six normal male volunteers, pretreated with 500 mg of lithium carbonate, who were undergoing maximal water diuresis. 2. This dose of ANG II caused a circulating increment within the physiological range (27 +/- 4 to 48 +/- 9 pmol/l). 3. Compared with placebo, ANG II caused a significant fall in urinary sodium excretion (113 +/- 13 to 82 +/- 10 mumol/min). This antinatriuretic effect occurred without a fall in creatinine clearance (107 +/- 3 versus 113 +/- 3 ml/min). 4. ANG II caused a significant fall in fractional lithium clearance (28 +/- 2 to 23 +/- 2%). This may indicate a proximal tubular effect of ANG II. 5. ANG II also reduced fractional distal delivery [(sodium clearance plus free water clearance) divided by creatinine clearance], another measure of proximal tubular outflow. A parallel change in these two separate markers of proximal function supports an action of ANG II at this nephron segment. 6. Furthermore, the antinatriuretic effect of ANG II was unlikely to be due to stimulation of aldosterone secretion because (a) the fall in sodium excretion was temporally dissociated from the rise in aldosterone secretion, (b) potassium excretion also tended to fall during ANG II infusion and (c) aldosterone has a distal nephron effect, while, in this study, proximal nephron fractional reabsorption of sodium increased and distal nephron fractional reabsorption of sodium was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The effect of angiotensin II and noradrenaline alone and in combination on renal sodium excretion in man.

1. The renin-angiotensin-aldosterone-system is important for the maintenance of sodium balance in man. Recent animal evidence suggests the angiotensin II can modulate the effect of the renal sympathetic nervous system on renal function. We have investigated the possible interaction of physiological doses of angiotensin II and noradrenaline on sodium excretion in man. 2. Seven normal volunteers were studied on four occasions during maximum water diuresis sustained by oral hydration. Samples were obtained during a baseline and four subsequent 20 min periods (A-E). Placebo or noradrenaline was infused over periods B-E, and angiotensin II infused over period C. 3. There was no change in systemic blood pressure, heart rate or creatinine clearance caused by infusion of either angiotensin II, noradrenaline or both in combination. 4. Noradrenaline alone caused a significant fall in absolute and fractional sodium excretion. Angiotensin II when infused with placebo caused a 37% fall in absolute sodium excretion and a 32% fall when infused with noradrenaline (no significant difference between the 2 days). Similar changes were seen for urinary flow and fractional sodium excretion. 5. We have therefore found no evidence to support a postsynaptic interaction of low doses of angiotensin II and noradrenaline on renal sodium excretion in man.

Adult↗
PubMed1989

Systemic beta-adrenoceptor responses to salbutamol given by metered-dose inhaler alone and with pear shaped spacer attachment: comparison of electrocardiographic, hypokalaemic and haemodynamic effects.

1. Seven normal subjects were given cumulative doubling doses of inhaled salbutamol either by metered-dose inhaler (MDI) alone, or in conjunction with a pear shaped spacer attachment (PSS). Dose increments were made every 20 min from 100 micrograms to 2000 micrograms. 2. Plasma potassium (K), electrocardiographic (ECG) and haemodynamic (HR, SBP and DBP) responses were measured at each dose increment. 3. There were falls in K (as mean and 95% CI) in response to salbutamol (P less than 0.001): 3.70 mmol l-1 (3.46-3.95) to 3.20 mmol l-1 (2.91-3.49) MDI, 3.78 mmol l-1 (3.61-3.95) to 3.18 mmol l-1 (3.06-3.30) PSS. 4. Salbutamol produced marked ECG effects including T wave flattening (P less than 0.001): 0.46 mV (0.24-0.68) to 0.22 mV (0.07-0.37) MDI, 0.50 mV (0.23-0.77) to 0.24 mV (0.07-0.41) PSS; and Q-Tc interval prolongation (P less than 0.001): 0.382 s (0.372-0.392) to 0.409 s (0.397-0.421) MDI, 0.378 s (0.358-0.398) to 0.410 s (0.388-0.432) PSS. U waves occurred in five subjects with MDI and in four with PSS. S-T segment depression was present in two subjects with MDI and in three with PSS. These changes were not however associated with ventricular extrasystoles. There were also significant chronotropic effects (P less than 0.001): 63 beats min-1 (57-70) to 79 beats min-1 (69-89) MDI, 58 beats min-1 (53-63) to 75 beats min-1 (69-81) PSS. 5. Comparison of dose-response curves for MDI alone and with PSS showed no significant differences, for any of the variables measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Noradrenaline attenuates the natriuretic effect of atrial natriuretic factor in man.

1. The effects of noradrenaline (0.025 micrograms kg-1 min-1) and atrial natriuretic factor (0.04 micrograms kg-1 min-1) alone, and in combination, were studied in eight healthy salt replete men. 2. Atrial natriuretic factor increased urinary sodium excretion and flow rate without changing glomerular filtration rate or systemic haemodynamics. 3. Noradrenaline decreased urinary sodium excretion without changing glomerular filtration rate, urinary flow rate or systemic haemodynamics. 4. When atrial natriuretic factor was administered against a background infusion of noradrenaline the natriuretic response to the peptide was significantly attenuated. 5. Further analysis showed that this attenuation was due to the additive antinatriuretic effect of noradrenaline rather than to a specific interaction between atrial natriuretic factor and noradrenaline. 6. The possible significance of this interplay between noradrenaline and atrial natriuretic factor is discussed in the context of experimental evidence for an important role of the sympathetic nervous system in modulating the renal effects of atrial natriuretic factor in animals.

Adult↗
PubMed1989

Evidence for a proximal and distal nephron action of atrial natriuretic factor in man.

The intrarenal mechanism of action of atrial natriuretic (ANF) remains uncertain. Animal work suggests that part of the natriuretic effect of ANF may be due to inhibition of proximal and distal nephron sodium reabsorption and we now present evidence for similar effects of ANF in man. Six sodium replete normal male volunteers were studied during maximal water diuresis. Lithium clearance was used to assess segmental nephron function. ANF infusion caused a significant increase in fractional lithium clearance (FELi) compared to placebo infusion. A similar change in fractional distal delivery, a conventional marker of proximal tubular outflow, also occurred during ANF infusion independently corroborating the increase in FELi. These findings suggest that ANF inhibits whole-kidney fractional proximal tubular sodium reabsorption in man. Evidence is also presented to show that ANF depresses distal nephron fractional sodium reabsorption as evaluated both by the lithium method and by estimation of solute-free water clearance.

Absorption↗