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Biomedical subjects

I B Squire

Publications and source records attributed to I B Squire.

15 recordsLinked to original sources
PubMed1994

Anticardiolipin antibodies in an unselected stroke population.

A pathogenetic role in thrombotic disease, particularly in young people, has been postulated for anticardiolipin antibody (ACA). We have carried out a prospective controlled study of 262 unselected patients with acute stroke and 226 controls to assess the prevalence and relation to age and vascular risk factors of ACA. Titres of IgG, IgA, or IgM ACA were above the upper normal limit in 38% of patients. The proportions of patients and controls with raised titres did not differ significantly (13 vs 8% IgG, 22 vs 29% IgA, 11 vs 7% IgM). IgG titres were higher among patients than among controls (mean 3.88 vs 2.86 u/mL [95% CI for difference 0.62-0.87], p = 0.0004), whereas IgA and IgM titres were lower in patients than in controls (IgA 4.82 vs 5.98 u/mL [1.12-1.60], p = 0.01; IgM 3.00 vs 3.64 u/mL [1.01-1.45], p = 0.04). However, within age tertiles the only significant difference between patients and controls for IgG ACA was in the oldest tertile. Analysis by number of risk factors for stroke showed a significant difference between the groups only for subjects with one risk factor. IgA and IgM ACA titres were higher among controls only in those with no vascular risk factors. We found no evidence to support the hypothesis that ACA is an independent risk factor for stroke in young people. The increase in IgG titre with age and number of vascular risk factors in stroke patients suggests that ACA may be a non-specific accompaniment of vascular disease. Routine testing for ACA in stroke patients is not justified.

Acute Disease↗
PubMed1994

Haemodynamic response and pharmacokinetics after the first dose of quinapril in patients with congestive heart failure.

1. Twenty-four elderly patients with stable, chronic congestive heart failure, NYHA II-IV, requiring addition of an ACE inhibitor to their existing therapy were randomised to receive double-blind a single dose of quinapril 2.5 mg p.o. or matching placebo after 24-48 h supervised diuretic withdrawal. 2. The effect of treatment on resting supine blood pressure, heart rate, plasma angiotensin converting enzyme (ACE) and circulating plasma renin activity was compared between groups over the first 24 h after dosing. The pharmacokinetic profiles of quinapril and the active metabolite quinaprilat were determined. 3. Compared with placebo, quinapril caused a statistically significant but modest fall in blood pressure from 3 to 10 h post dose. The maximum fall of 12 mm Hg (95% C.I. 5.4-18.5) was seen at approximately 5 h. Circulating ACE activity was 40% inhibited within 1 h. Maximum ACE inhibition (83.6%, 95% C.I. 76.7-90.5) was observed at 3 h. ACE remained 60% inhibited at 24 h post dose. tmax for quinapril was seen at 2.6 +/- 1.2 h. while tmax for quinaprilat was at 3.6, +/- 0.8 h. 4. Treatment with quinapril was associated with a significant rise in plasma renin activity (PRA) of 8.83 ng AI ml-1 h-1 (95% C.I. 0.30-17.96) compared with placebo. 5. Compared with placebo, quinapril 2.5 mg inhibits plasma ACE by over 60% for 24 h and reduces blood pressure for at least 10 h in patients with stable, chronic congestive heart failure. The blood pressure fall, although moderate and well tolerated, is more sustained than previously described for quinapril in heart failure.

Aged↗
PubMed1993

Blood pressure response to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibitors improve survival in heart failure and delay progression to clinical heart failure in patients with left ventricular dysfunction after myocardial infarction. Increasing numbers of older patients are being considered for such treatment. However, there are reports of excessive and prolonged decreases in blood pressure (BP) after the first dose of some ACE inhibitors. We have studied the hemodynamics, pharmacokinetics, and neurohumoral responses to the first dose of oral captopril 6.25 mg, enalapril 2.5 mg, perindopril 2.0 mg, intravenous enalaprilat 1.5 mg, and perindoprilat 1.0 mg, compared with oral or intravenous placebo in 6 parallel groups of 12 elderly patients each with moderate-to-severe (New York Heart Association classes II-IV) heart failure. Oral dosing with active drugs led to different temporal responses. After captopril, there was an early short-lived decrease in BP. Enalapril led to a later long-lasting decrease, but perindopril was not different from placebo. Intravenous enalaprilat and intravenous perindoprilat each lowered BP to a similar extent. The doses of drugs used appeared to be comparable because plasma ACE inhibition was similar following perindopril or enalapril and also comparing perindoprilat and enalaprilat. These studies indicate that oral ACE inhibitors have different profiles of acute BP changes after the first dose. The explanation is not clear, but could include physicochemical differences in the interaction between prodrug ester and diacid metabolites leading to differences in tissue distribution and local enzyme inhibition.

Aged↗
PubMed1993

Analysis of biogenic amines in plasma of hypertensive patients and a control group.

Procedures were developed for the determination of 17 circulating amines using gas chromatography-negative ion chemical ionisation mass spectrometry. The amines were quantified against their appropriate deuterated isotopomers. The mean concentrations and ranges of catecholamines and trace amines were high compared with previous studies. In comparison with nonhypertensives, plasma from hypertensives had higher concentrations of the following amines: noradrenaline (t = 4.0%); normetanephrine (t = 6.1%) and metanephrine (t = 1.9%). There were no significant differences between 5HT levels in plasma from hypertensives and controls. The following trace amines could be detected in variable amounts in plasma: p-tyramine, m-tyramine, p-octopamine, m-octopamine, p-synephrine, m-synephrine, and salsolinol. The trace amines melatonin, N-acetyl 5HT, tryptamine, 6-hydroxymelatonin and 5-methoxytryptamine could not be detected in plasma with limits of detection lying in the range 20-100 pg ml-1.

Biogenic Amines↗
PubMed1993

Angiotensin-converting enzyme inhibitors in heart failure: blood pressure changes after the first dose.

Angiotensin-converting enzyme (ACE) inhibitors prevent the formation of angiotensin II in the circulation and a range of tissues. ACE inhibitors not only are effective, well-tolerated antihypertensive drugs but also improve symptoms and signs in patients with congestive cardiac failure. In addition, they improve long-term survival in these latter patients. Although ACE inhibitors are relatively free of side effects in patients with heart failure, hypotension after the first dose has been reported that may lead to symptomatic renal, cardiac, or cerebral hypoperfusion. Most reports have been uncontrolled and anecdotal. We report a double-blind placebo-controlled study in a parallel group of patients with cardiac failure (New York Heart Association classes II through IV). In total, 72 patients (6 groups of 12) were studied after either placebo, captopril, 6.25 mg, enalapril, 2.5, or perindopril, 2 mg orally, enalaprilat 1.5 mg, or perindoprilat, 1.0 mg intravenously. The blood pressure responses differed between the groups, with a short-lived early fall after captopril and a long-lasting fall after enalapril, whereas perindopril was no different from placebo. There was no significant difference between the two active intravenous regimens. Plasma ACE measurements suggested that the relative doses used were at least comparable. Further studies are in progress to investigate the mechanisms underlying the differential hemodynamic responses and also to explore the clinical relevance to safety and efficacy in the management of heart failure.

Acetylcholinesterase↗
PubMed1993

The experiences of an acute stroke unit--implications for multicentre acute stroke trials.

The suitability of 200 consecutive patients admitted to a newly established acute stroke unit was assessed for participation in two multicentre trials currently in their pilot phase: the International Stroke Trial of aspirin and heparin, and the Multicentre Acute Stroke Trial of streptokinase versus placebo. Of the 200 patients (74 men, 126 women, mean age 71 years), 96% had cerebral CT, and 94% had a final diagnosis of cerebrovascular disease. Overall, 50% of patients presented within 6 hours and 70% within 12 hours of the onset of ictus. A total of 113 patients (56.5%) were potentially eligible for trial treatment with aspirin/heparin. Only 9 patients (4.5%) were eligible for streptokinase treatment: 50% were excluded because they presented after 6 hours; 23% had a previous stroke with clinical sequelae and 23% had severe systemic illness. Forty eight per cent of patients had more than one exclusion criterion. The potentially high enrollment rates in trials of antithrombotic agents contrast with the restricted recruitment for trials of streptokinase, emphasising the need for multiple centres to achieve useful study enrollment.

Adult↗
PubMed1992

The clinical pharmacology of ACE inhibitors: evidence for clinically relevant differences?

1. Potential differences among ACE inhibitors include pharmacokinetic and pharmacodynamic factors. The presence of a sulfhydryl group conferring antioxidant properties, the administration as a pro-drug to delay the onset and prolong the duration of haemodynamic effects, and the route of elimination are examples of possible differences. 2. Adverse effects of ACE inhibitors may be mediated by effects on bradykinin metabolism at tissue sites, which may be separable from haemodynamic responses mediated largely by angiotensin II withdrawal. 3. Clinically important differences between ACE inhibitors in their adverse event profile have yet to be proven. Evidence is emerging that plasma ACE inhibition and haemodynamic responses are separable, and this may indicate the potential for other organ-specific effects to differ among ACE inhibitors. 4. At present, however, the greatest distinguishing features for one compound vs another are the time to onset and the duration of action, which determine the frequency of administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Neuromuscular blocking and autonomic effects of vecuronium and atracurium in the anaesthetized cat.

The effects of vecuronium and atracurium on neuromuscular transmission, on the responses of the heart rate to vagal stimulation and on the responses to preganglionic stimulation of the nictitating membrane were compared in the chloralose-anaesthetized cat. Vecuronium was four times more potent than atracurium as a neuromuscular blocking agent, whereas the two compounds had similar potencies in blocking the effects of stimulation of the cardiac vagus. The vagal/neuromuscular ratios measured at 50% inhibition were 96 for vecuronium and 25 for atracurium. Vecuronium possessed a slightly shorter recovery time than atracurium and shorter duration of action on the soleus muscle. The onset times of the two compounds were not significantly different. Both compounds had longer time-courses of action than suxamethonium. Very large doses of vecuronium decreased the responses of the preganglionic stimulation of the nictitating membrane, suggesting that at high doses the compound possesses ganglion blocking activity. Large doses of atracurium also decrease the nictitating membrane responses and, in some cats, contractions of the nictitating membrane associated with increases in heart rate and arterial pressure were observed.

Anesthesia, General↗