Biomedical subjects
M J Kendall
Publications and source records attributed to M J Kendall.
Therapeutic progress--review. XXIX. Is there a role for low-dose angiotensin converting enzyme inhibitors in the treatment of mild to moderate hypertension?
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Effect of nifedipine on serum theophylline concentrations and asthma control.
The effect of adding slow release nifedipine to oral theophylline has been studied in eight patients with stable but symptomatic asthma, a double blind placebo controlled crossover protocol being used. No change in asthma control occurred during the nifedipine treatment period as assessed by serial peak flow measurements and symptom scores. Serum theophylline concentrations were significantly lower after nifedipine than after placebo (6.8 v 9.7 micrograms/ml) and in three patients were well below the therapeutic range (less than 4 micrograms/ml).
Captopril reduces the renal response to intravenous atrial natriuretic peptide in normotensives.
The interaction between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone (RAA) system was studied in 6 healthy volunteers using the angiotensin-converting-enzyme (ACE) inhibitor, captopril. Each volunteer received, on separate occasions in random order, 48 hours treatment with a) low-dose captopril (6.25 mg twice daily), b) 'high-dose' captopril (25 mg twice daily) and c) placebo prior to an infusion of synthetic human ANP (99-126). Resting plasma ANP levels were significantly (P less than 0.01) higher on treatment with 'high-dose' captopril when compared with low-dose captopril or placebo. 'High-dose' captopril reduced mean arterial blood pressure (BP) and significantly (P less than 0.01) reduced the natriuretic response to the human ANP infusion. These results support the hypothesis that ACE is involved in ANP metabolism. The reduced renal response to ANP during treatment with captopril may reflect the dependence of ANP on adequate renal perfusion pressure and angiotensin II levels to exert its natriuretic effect.
Calcium antagonists and the kidney.
Calcium antagonists are frequently used to treat patients with hypertension or ischaemic heart disease. These patients often have renal impairment, so the effects of calcium antagonists on the kidney are important. The effects of calcium antagonists on renal haemodynamics are variable and depend on the state of the patient or animal and the dose of calcium antagonist used. Calcium antagonists cause natriuresis and diuresis by a mechanism which is not fully understood, but which is probably not directly due to the effects of calcium antagonists on renal haemodynamics. The diuretic effect may be useful in limiting the oedema which would otherwise be induced by vasodilator therapy. The effects of calcium antagonists on peripheral renin activity are unpredictable: renin release may be affected directly, as well as via haemodynamic effects. The pharmacokinetics of calcium antagonists are little changed in renal failure, since these drugs are metabolised in the liver. Calcium antagonists appear to be safe and useful treatments for patients with hypertension or ischaemic heart disease and co-existing renal impairment.
The intra- and inter-subject variability of nifedipine pharmacokinetics in young volunteers.
Plasma concentrations of Nifedipine were measured following single oral doses of Nifedipine Slow Release (Adalat Retard) on three separate occasions to young, healthy volunteers of both sexes. Intra- and inter-subject variability were assessed by comparing the pharmacokinetic parameters, AUC, Cmax and T50%AUC. Interindividual variability was less than that observed in other studies with the beta-blockers, metoprolol and propranolol and there was no evidence of differences between the sexes.
Change in plasma immunoreactive atrial natriuretic peptide during sequential ultrafiltration and haemodialysis.
Plasma immunoreactive human atrial natriuretic peptide (Ir-ANP) levels were measured in eight patients with chronic renal failure who were volume-expanded and during treatment by sequential ultrafiltration and haemodialysis. One patient was studied at two separate treatment sessions. Plasma Ir-ANP levels were raised in all patients (mean +/- SE 184 +/- 44 pmol/l, n = 9) compared with healthy controls (11 +/- 1.4 pmol/l), but showed considerable inter-patient variability. Plasma Ir-ANP levels fell with fluid removal during ultrafiltration (123 +/- 30 pmol/l, n = 9, P less than 0.02) and again as fluid was removed during haemodialysis (76 +/- 20 pmol/l, n = 9, P less than 0.02). Seven patients studied 48 h later, before their next dialysis treatment, had regained weight and showed a coincident rise in circulating plasma Ir-ANP (130 +/- 33 pmol/l, n = 7). Our data would support the hypothesis that the secretion of ANP is determined by volume or by a stimulus related to volume. However, it does not exclude the possibility that a factor other than extracellular fluid volume expansion contributes to the raised plasma Ir-ANP levels in chronic renal failure.
Potentiation of the adverse effects of intravenous terbutaline by oral theophylline.
We have studied the influence of therapeutic plasma concentrations of theophylline on some of the unwanted responses to intravenous terbutaline in normal subjects. There was a significantly greater fall in serum potassium and rise in plasma glucose, pulse rate and systolic blood pressure in response to an intravenous infusion of terbutaline when theophylline was present compared with when terbutaline was given alone. These drugs are commonly used together in the treatment of acute asthma and potentiation of side effects may be hazardous. We suggest monitoring of the serum potassium when these drugs are used together during acute exacerbations of asthma.
Calcium antagonism--with special reference to diltiazem.
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Calcium antagonists and glycaemic control.
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Objective relief of vasospasm by glyceryl trinitrate in secondary Raynaud's phenomenon.
An objective response to topical glyceryl trinitrate was shown by digital plethysmography in a study of 17 patients with Raynaud's phenomenon. Improvement was significant (P less than 0.005) in those in whom the disease was secondary to an underlying connective tissue disorder. The response suggests that the effect of this drug is mediated locally.
Behçet's disease presenting as benign intracranial hypertension.
Two siblings with Behçet's disease presenting as benign intracranial hypertension are reported and the literature is reviewed. We suggest that raised intracranial pressure should be added to the clinical criteria considered for the diagnosis of Behçet's disease.
Sarcoidosis--a cause of steroid responsive total alopecia.
We present a case of sarcoidosis complicated by total alopecia and a myopathy occurring in a young West Indian woman. There was a very satisfactory response to oral steroids.
Calcium antagonists and chronic cardiac failure.
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Sodium transport across erythrocyte membranes in diabetes mellitus.
The activity of the erythrocyte ouabain sensitive Na/K ATPase pump was studied in 20 Type 1 diabetics, 15 Type 2 diabetics and 20 healthy controls. All diabetics were normotensive, caucasian and non-obese diabetics. The diabetics were assessed for retinopathy and had HbA1 estimated. The erythrocyte sodium concentration, membrane permeability to sodium and ouabain-sensitive sodium efflux rate constant (ERCos) were determined. The Type 1 diabetics had a significantly reduced ERC, mean +/- SD 0.198 +/- 0.028 hr-1 vs control 0.264 +/- 0.054 hr-1 (p less than 0.001). A similar reduction in ERCos was seen in the Type 2 diabetics when compared to controls (0.229 +/- 0.059 hr-1 p less than 0.005). There was also a significant difference between the 2 groups of diabetics (p less than 0.05). There was no significant difference in intracellular sodium concentrations. Membrane permeability was reduced in the Type 1 diabetics (3.69 +/- 0.79 mmol/kg dry wt/hr) compared to the control group (4.56 +/- 0.79 mmol/kg dry wt/hr, p less than 0.01). Diabetic control (HbA1) was positively correlated with ERCos, but no significant differences were seen in the ERCos between complicated and uncomplicated Type 1 diabetics. In vitro studies of normal erythrocytes did not show an effect on pump activity of increasing glucose or insulin concentration during a preincubation study. These results demonstrate that there is a reduction in activity of the ouabain-sensitive Na/K ATPase pump and a reduction in membrane permeability on the diabetic erythrocyte which is most marked in Type 1 diabetics.
The effects of selective and non-selective inhibition of cyclo-oxygenase on frusemide-stimulated natriuresis.
The relative potency of four non-steroidal anti-inflammatory drugs (NSAIDs) - indomethacin, flurbiprofen, sulindac and piroxicam - in inhibiting frusemide-stimulated natriuresis and creatinine clearance was investigated in a placebo controlled cross-over study using healthy volunteers. All four drugs tested significantly inhibited the action of frusemide and they were equipotent in their effects. If it is accepted that sulindac is renal sparing with respect to inhibition of prostaglandin synthesis, our observations raise two possibilities concerning the underlying mechanism of antagonism: a) that inhibition of renal prostaglandin synthesis is not important; b) that sulindac interacts with frusemide in a manner different from other NSAIDs.
A clinical review of calcium antagonists in acute myocardial infarction.
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Downgrading of biochemical and cardiovascular responses to an intravenous infusion of terbutaline following chronic treatment with oral terbutaline.
Beta 2-agonists are known to cause a range of unwanted biochemical and cardiovascular responses. The present study was designed to investigate the effect of chronic exposure to beta 2-stimulation on the magnitude of these responses produced by an acute challenge with a beta 2-agonist. In this single blind placebo controlled study in six healthy male volunteers, we have compared the effects of chronic dosing with either oral terbutaline (5 mg three times daily for two weeks) or placebo on a number of these responses produced by an intravenous infusion of terbutaline (6 micrograms per kilogram over 1 hour). The infusion was given twenty-four hours after the last dose of oral terbutaline or placebo. The rise in pulse rate, systolic blood pressure and plasma glucose and the fall in serum potassium during terbutaline infusion, although still demonstrable, were significantly reduced following treatment with oral terbutaline compared to placebo. This suggests downgrading of beta-receptor function after chronic beta 2-stimulation.