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Biomedical subjects

P F Semple

Publications and source records attributed to P F Semple.

At least 19 recordsLinked to original sources
PubMed1995

Putative mechanisms of cough after treatment with angiotensin converting enzyme inhibitors.

BACKGROUND: A dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors, even if it is not particularly serious. Controlled studies have suggested that the incidence may eventually be as high as 20% and the problem seems to occur much more often in women. MECHANISM OF ACE INHIBITOR COUGH: The mechanism of the cough associated with ACE inhibitor treatment is unrelated to inhibition of the renin-angiotensin system because treatment with angiotensin receptor blockers and renin inhibitors has not caused similar problems. Other substrates of ACE have been implicated, and the side effect has been linked in particular to an accumulation of bradykinin or tachykinins in the airways with consequent stimulation of vagal afferents that subserve the cough reflex, particularly the non-myelinated or C fibres. Some of the effects of bradykinin in particular may be due to secondary activation of prostaglandins (PG), especially PGE2 and PGI2. Anecdotal evidence that cyclooxygenase inhibitors prevent the cough has not been sustained in well controlled clinical trials, but recent evidence suggests that inhaled cromoglycate may have a significant inhibitory effect. The mechanism of action of cromoglycate is not well understood but evidence of inhibition of local neural reflexes has been inferred, mostly from animal studies. The observation seems unlikely to have much practical benefit for it is difficult to envisage routine use of an inhaled agent to prevent a drug side effect. The question of whether ACE inhibitors are safe in patients with asthma is still open, and most rechallenge studies have shown little effect on lung function. Data from one large-scale surveillance study suggest that a few individuals may experience dyspnoea and wheezing but no causal relationship has been established. CONCLUSION: Delineation of the mechanism of the ACE inhibitor cough may lead to a better understanding of the mechanism of cough in inflammatory airways disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Renal artery stenosis managed by Palmaz stent insertion: technical and clinical outcome.

OBJECTIVE: To assess the technical and clinical outcome of Palmaz renal artery stent insertion in patients with renal artery stenosis. DESIGN: Twenty-nine patients with radiological evidence of renal artery stenosis and hypertension (16 patients, mean +/- SD diastolic blood pressure 100.5 +/- 8.16 mmHg) and/or renal impairment (17 patients, mean +/- SD serum creatinine 376 +/- 169 mu mol/l) were referred for radiological intervention. Of these, 22 had ostial atheromatous lesions, six had atheromatous non-ostial lesions and one patient had fibromuscular dysplasia. Palmaz stent insertion was performed where either previous or concomitant percutaneous transluminal renal angioplasty (PTRA) had been unsuccessful. Technical success was defined primarily as <30% residual stenosis. A prospective radiological and clinical follow-up was performed and the results compared with the outcome following PTRA alone in a similar group of patients from our centre. RESULTS: Immediate technical success was achieved in all 29 patients. Follow-up angiography in 24 patients after a mean of 7 months showed restenosis in four patients. The hypertension was not 'cured' in any patient; a blood pressure fall was observed in seven patients (44%) and no change in the remaining nine subjects (56%). Renal function improved in four patients (24%), two of whom had angiotensin converting enzyme inhibitor-exacerbated renal impairment. This compares with an immediate technical success of 81% for PTRA alone, with cure in 50% and improvement in 32% of patients with hypertension and improvement in renal function in 64.7% of patients with renal impairment. CONCLUSIONS: Palmaz renal artery stent insertion has a higher technical success rate than PTRA, but the clinical improvement is disappointing in our patient population.

Adult↗
PubMed1994

Hypertension: investigation, assessment and diagnosis.

Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes.

Blood Pressure Determination↗
PubMed1991

Renal responses to angiotensin II infusion in early type 1 (insulin-dependent) diabetes.

The renal response to infusion of sub-pressor doses of angiotension II was examined in nine euglycaemic Type 1 (insulin-dependent) diabetic patients with diabetes of short duration and nine non-diabetic control subjects. Plasma concentrations of angiotensin II and of free insulin were similar in both groups at baseline and during angiotensin II infusion. Glomerular filtration rate (Inutest clearance) fell to a similar extent during angiotensin II infusion in both groups (diabetic 116(SE 5) to 102(5) ml min-1 1.73-m-2; control 113(6) to 100(5) ml min-1 1.73-m-2). There was a large dose-dependent fall in effective renal plasma flow (p-aminohippurate clearance) during angiotensin II infusion which was of similar magnitude in both groups (diabetic; 694(46) to 521(21) ml min-1 1.73-m-2; control 665(41) to 498(30) ml min-1 1.73-m-2). The absolute and the fractional rates of urinary excretion of sodium were both lower in the diabetic group throughout the study, but there was a comparable antinatriuretic response to angiotensin II. Thus, the renal haemodynamic response to angiotensin II infusion is normal in early well-controlled Type 1 diabetes. Differences were found in the renal handling of sodium, which could not be related to altered renal tubular responses to angiotensin II or to peripheral hyperinsulinaemia.

Adult↗
PubMed1990

Blood pressure, left ventricular mass and intracellular calcium in primary hyperparathyroidism.

1. Blood pressure, left ventricular mass and platelet cytosolic free calcium concentrations were measured in 23 patients with untreated primary hyperparathyroidism, 30 normotensive control subjects and 23 control subjects matched for age, sex and blood pressure. In 12 patients measurements were repeated after parathyroidectomy. 2. Patients with primary hyperparathyroidism had significantly elevated blood pressures (139 +/- 6/86 +/- 3 mmHg, mean +/- SEM) compared with control subjects (125 +/- 2/78 +/- 1 mmHg), but high values persisted after hypercalcaemia was corrected. 3. Despite chronic extracellular hypercalcaemia, intracellular free calcium levels were lower in patients with hyperparathyroidism than in controls matched for age, sex and blood pressure (median concentrations 81.5 nmol/l vs 93 nmol/l, 95% confidence interval 0.1 to 20.1; P less than 0.05) and values tended to increase after parathyroidectomy. 4. Left ventricular mass index was increased in the primary hyperparathyroid group as compared with control subjects matched for age, sex and blood pressure (123 g/m2 vs 100 g/m2, 95% confidence interval -36.1 to -3.1; P = 0.03). Parathyroidectomy resulted in a small reduction of the left ventricular mass index (123.5 g/m2 vs 104 g/m2, 95% confidence interval 46.5 to 2.5; P = 0.1) but no change in blood pressure. 5. Hypertension and left ventricular hypertrophy in primary hyperparathyroidism are associated with relatively low levels of free calcium in platelets.

Adult↗
PubMed1989

Platelet cytosolic free calcium in essential hypertension: responses to vasopressin.

1. Resting and stimulated free calcium concentrations have been measured in platelets loaded with the fluorescent probe quin2 from 30 patients with essential hypertension and from 30 age-matched controls. 2. Cytosolic free calcium concentrations were 94.6 +/- 2.7 (mean +/- SEM) in the hypertensive group and 91.7 +/- 2.8 nmol/l in the normotensive group, the difference was not significant. 3. Arginine vasopressin caused a transient increase in platelet free calcium concentration in all subjects. In the presence of extracellular calcium the increase was significantly higher in the control subjects than in the hypertensive patients (P = 0.005). In the absence of extracellular calcium, arginine vasopressin caused much smaller increases, and there was then no difference between the responses of the two groups. 4. Platelet free calcium concentrations were measured again in 13 patients after 8 weeks treatment with either verapamil (n = 6) or atenolol (n = 7). The reductions in systolic pressure after drug treatment were correlated with the changes in cytosolic free calcium concentrations (r = 0.75, P less than 0.01).

Adult↗
PubMed1989

Hypokalaemia in alcoholics.

Hyponatraemia has been described in beer drinkers and hypokalaemia resulting from increased levels of aldosterone is well recognised in patients with cirrhosis and ascites. We have encountered episodes of hypokalaemia in alcoholics accompanied by normal or increased serum concentrations of sodium. Despite a resemblance to syndromes of mineralocorticoid excess, increased levels of aldosterone and other mineralocorticoids were not found.

Adrenal Cortex Hormones↗
PubMed1989

Divalent cation-induced interconversion of hepatic angiotensin receptor subtypes.

The effects of divalent cations on the hepatic angiotensin receptor have been investigated using radioligand binding methods. With a plasma membrane-enriched fraction from rat liver, a total binding capacity for angiotensin peptides of 0.5 pmol/mg of membrane protein was observed. In the absence of divalent cations, almost all of these sites showed low affinity (KD, 11.25 nM) for angiotensin II. In the presence of Ca2+, there was a concentration-dependent increase in the proportion of sites with high affinity (KD, 0.94 nM) for angiotensin II. Mg2+, Sr2+, and Ba2+ were less effective in this respect, although Mg2+ also modified affinity of the high affinity subtype. Monovalent cations (Na+, Cs+, and K+) had little effect on angiotensin binding. Both receptor subtypes showed high and approximately equal affinity for sarcosine1-analogues of angiotensin II and 10-fold lower and equal affinity or Ile7-angiotensin III. The low affinity subtype appeared to be more sensitive to N-terminal deletions in the peptide. Interconversion of receptor subtypes could be prevented by 5'-guanylylimidodiphosphate, La3+, diltiazem, and verapamil. The results show that the hepatic angiotensin receptor can exist in high and low affinity states in vitro and that the proportion in each state can be modified by divalent cations, guanine nucleotides, and some Ca2+ antagonist drugs.

Angiotensin II↗
PubMed1989

Severe hypotension with bradycardia during renin inhibition with H142 in sodium deplete man.

A healthy sodium depleted subject received, on separate occasions, intravenous infusions of the renin inhibitor H142 at doses of 1.0, 2.5 and 5.0 mg/kg/h. The two lower doses of H142 produced dose-dependent reduction of both systolic and diastolic pressure associated with an increase in heart rate. The highest dose of H142 produced profound hypotension and bradycardia, both during drug infusion in the supine position, and again later, on return to standing, after H142 was stopped. An increase in plasma adrenaline, but not noradrenaline, was associated with this dose of H142. The subject differed from others studied in a randomised controlled trial of H142 at doses of 1.0 and 2.5 mg/kg/h in having the highest basal circulating plasma angiotensin II concentrations during sodium depletion, and in developing a clear reduction in systolic as well as diastolic pressure. The profound hypotensive response at the highest dose of H142 may represent an idiosyncratic response to the drug. Alternatively, and perhaps more likely, it may be a result of a reduction of angiotensin II concentrations in plasma or other tissues, with loss of arteriolar constriction, loss of facilitation of sympathetic activity, withdrawal of vagal inhibition, dilatation of capacitance vessels, or a combination of these events. Subsequent activation of the Bezold-Jarisch reflex is a possibility. The late fall in blood pressure, after H142 was stopped, and when circulating plasma angiotensin II concentrations had returned to normal, suggests that this response may have involved an effect of the inhibitor on renin in a site other than blood.

Adult↗
PubMed1988

Bronchial hyperreactivity in patients who cough after receiving angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors. Cough associated with converting enzyme inhibitors may be a variant of the cough in asthma.

Adult↗