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Biomedical subjects

A R Lorimer

Publications and source records attributed to A R Lorimer.

At least 55 records · Page 3Linked to original sources

Comparison of enalapril and atenolol in mild to moderate hypertension.

PURPOSE: Short-term therapy with angiotensin converting enzyme (ACE) inhibitors for hypertension is effective and well tolerated, and compared with beta blockers, may cause fewer adverse reactions. Furthermore, enalapril has been observed to have a greater effect on systolic blood pressure than beta blockers. We therefore decided to compare the ACE inhibitor enalapril and the beta blocker atenolol as monotherapy in a double-blind study of patients with mild to moderate hypertension. PATIENTS AND METHODS: After a four-week placebo run-in period, 162 patients were allocated randomly to receive atenolol (50 to 100 mg daily) or enalapril (20 to 40 mg daily) for 12 weeks. To assess the influence of these drugs on quality of life, a series of psychologic tests was performed, and a subset of patients also underwent treadmill exercise and pulmonary function tests. RESULTS: In 147 patients who completed the study, enalapril reduced supine blood pressure by 19/12 mm Hg, compared with 9/7 mm Hg for atenolol (p less than 0.001/p less than 0.005). The modest blood pressure response to atenolol was not due to poor compliance. A target blood pressure of 140/90 mm Hg or less was achieved by 35 percent of enalapril-treated atenolol (p less than 0.01). The frequency and severity of adverse effects with the two drugs were similar, and few important differences emerged from the quality-of-life assessments. CONCLUSION: At the doses used, enalapril induced a greater short-term blood pressure response than atenolol; long-term studies of its safety and efficacy are required.

Adolescent↗

Effect of combined therapy with bezafibrate and cholestyramine on low-density lipoprotein metabolism in type IIa hypercholesterolemia.

This study was designed to examine the influence of combined therapy with bezafibrate and cholestyramine on plasma lipids and on the metabolism of low-density lipoprotein (LDL). Twenty-one type II hyperlipidemic subjects were treated with bezafibrate alone or in combination with cholestyramine. A 17% fall in plasma cholesterol was seen with bezafibrate, and addition of cholestyramine produced an additional 9% reduction in this lipid. The effectiveness of the combination therapy was mediated through a 47% decrement in very-low-density lipoprotein (VLDL) cholesterol, a 37% reduction in LDL cholesterol, and a 15% increase in the level of that lipid in high-density lipoprotein (HDL). Plasma triglyceride fell 43% when bezafibrate was given alone, and did not change further when cholestyramine was added. The metabolism of LDL was examined in nine individuals to determine the mechanism underlying these changes. No significant modification in LDL synthetic rate was incurred with either drug regimen, whereas the fractional catabolic rate of LDL via the receptor pathway rose by 66% with bezafibrate alone and by 79% (compared to baseline) following the addition of cholestyramine. Plasma HDL rose during bezafibrate therapy due to an increase in the HDL3 subfraction. Compositional analysis of LDL showed a reduction in cholesterol ester and an increase in triglyceride and phospholipid during combined drug therapy. These results demonstrate that combined therapy with bezafibrate and cholestyramine markedly improves the lipoprotein profile in type II hyperlipidemia. The drugs appear to be complementary in their actions upon the LDL receptor pathway.

Adult↗

Pathophysiologic assessment of left ventricular hypertrophy and strain in asymptomatic patients with essential hypertension.

To investigate the significance of the electrocardiographic (ECG) pattern of left ventricular hypertrophy and strain, two groups of asymptomatic patients with essential hypertension were compared. The patients were similar in terms of age, smoking habit, serum cholesterol and blood pressure levels, but differed in the presence (Group I, n = 23) or absence (Group II, n = 23) of the ECG pattern of left ventricular hypertrophy and strain. Group I patients had significantly more episodes of exercise-induced ST segment depression (14 versus 4, p less than 0.05) and reversible thallium perfusion abnormalities (11 of 23 versus 3 of 23, p less than 0.05) despite similar exercise capacity and absence of chest pain. Nonsustained ventricular tachycardia was detected on 24 h ambulatory ECG monitoring in two patients in Group I, but no patient in Group II. Coronary arteriography performed in 20 Group I patients demonstrated significant coronary artery disease in 8 patients. This study has shown that there is a subgroup of hypertensive patients with ECG left ventricular hypertrophy and strain who have covert coronary artery disease. This can be detected by thallium perfusion scintigraphy, and may contribute to the increased risk known to be associated with this ECG abnormality.

Angiography↗

A comparison of amlodipine, verapamil and placebo in the treatment of mild to moderate hypertension. Amlodipine Study Group.

This is a double blind parallel group comparison in patients with mild-moderate hypertension, of amlodipine, verapamil and placebo. One hundred and sixty patients entered the double blind phase. In the amlodipine group the mean supine and standing systolic pressures at week 12 were respectively lowered from baseline by 11.9 mmHg and 11.3 mmHg more than for the placebo group (P = 0.0001). Diastolic blood pressures were also significantly reduced. With verapamil the mean supine and standing systolic blood pressure at week 12 were reduced by 7.7 mmHg and 8.3 mmHg more on verapamil than on placebo (P = 0.0083). Blood pressures of the amlodipine group were lower 24 hour post-dose than verapamil 12 hours post dose. The responder rates after eight weeks of double blind therapy were amlodipine 72.3%, verapamil 47.8% and placebo 32.6%. Body weight after verapamil increased by mean 0.9 kg, after amlodipine by 0.2 kg and after placebo decreased by 0.2 kg. Six patients were withdrawn because of adverse effects (3 amlodipine, 2 verapamil, 1 placebo). The number of patients with adverse effects possibly related to therapy were 22/53 for amlodipine, 19/54 for verapamil and 14/53 for placebo. Both drugs were, overall, well tolerated, effective and had no unexpected adverse effects.

Adult↗

24-hour control of blood pressure by once daily doxazosin: a multicentre double-blind comparison with placebo.

The antihypertensive efficacy of the new, once daily, alpha 1-adrenoceptor inhibitor, doxazosin, was compared with placebo in 40 patients with mild to moderate hypertension. Following a dose titration the mean final daily doxazosin dose in 20 patients was 13.1 mg. Through-the-day blood pressure control was assessed by frequent measurements during 24 h hospitalisation in the 9 th week of double-blind treatment compared with similar measurements made during a 2 week single-blind placebo run-in. Mean reductions in standing and supine systolic and diastolic blood pressure during doxazosin treatment were statistically significantly greater than during placebo treatment at most hourly time points during the 24 h post-dose period. Twenty-four post-dose the mean falls in standing and supine diastolic blood pressure during doxazosin treatment were statistically significant when compared with placebo. Adverse effects during doxazosin treatment were generally minor and were tolerated or disappeared with continued therapy. No patients were withdrawn from the study due to adverse effects. We conclude that once daily doxazosin provides smooth and effective blood pressure control throughout a 24 h post-dose period.

Adult↗

Comparison of amlodipine and verapamil in the treatment of mild to moderate hypertension.

One hundred sixty patients with mild to moderate essential hypertension entered this double-blind parallel group comparison of amlodipine, verapamil, and placebo. Sixteen centers from the United Kingdom and Norway participated in this multicenter study. Administration of amlodipine (2.5 mg with adjustment to 5.0 mg and to 10.0 mg o.d.) or verapamil (80 mg b.i.d. titrating to 160 mg b.i.d.) for 8 weeks to patients with mild to moderate hypertension was associated with clinically important and statistically significant decreases in both supine and standing blood pressures. After 8 weeks of double-blind therapy, the mean (amlodipine-placebo) difference in the falls from baseline in blood pressures measured 24 h postdose were -11.9/-7.0 mm Hg (supine) and -11.4/-6.3 mm Hg (standing). The corresponding figures were -7.7/-4.6 mm Hg and 8.3/-4.0 mm Hg for verapamil (12 h postdose). Mean reductions from baseline of the amlodipine group exceeded those of the verapamil group by 2-4 mm Hg for all pressure measurements, and this difference was statistically significant for diastolic blood pressures. Responder rates were 72, 48, and 33% for amlodipine, verapamil, and placebo, respectively. Mean doses at 8 weeks were 9.1 mg (amlodipine) and 296 mg (verapamil). There were no significant changes in pulse rate. Both active drugs maintained their antihypertensive effect through the day (0-12 h postdose) with amlodipine showing a sustained 24-h effect. Twenty-two patients in the amlodipine, 19 in the verapamil, and 14 in the placebo groups had side effects possibly related to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of a long-acting somatostatin analogue on portal and systemic haemodynamics in cirrhosis.

Current interest in the pharmacological manipulation of portal pressure centres on the long-acting somatostatin analogue SMS 201-995. Nine haemodynamically stable cirrhotic patients who had previously bled from oesophageal varices had wedged and free hepatic venous pressures and cardiac index measured, using a Swan-Ganz catheter, before and at 60, 120 and 180 min after beginning a 60-min infusion of 25 microgram/h of SMS 201-995. Seven clinically similar patients had the same measurements performed without SMS 201-995. In all patients cardiac index was found to decrease and systemic vascular resistance increase at 60 min, although heart rates and arterial blood pressures were unchanged. The group given SMS 201-995 was significantly different from the control group in sustaining a fall in wedged hepatic venous pressure and trans-hepatic venous gradient at 60 min. SMS 201-995 causes a fall in portal pressure without a significant systemic haemodynamic effect.

Adolescent↗

Thrombin and plasmin activity in coronary artery disease.

Basal plasmin and thrombin activity in plasma were assessed by radioimmunoassay of the fibrinogen derivatives containing the sequence B beta 15-42 and of fibrinopeptide A respectively in a cross sectional controlled study of men with coronary artery disease. Compared with healthy controls (n = 33) men with angiographically defined coronary artery disease (n = 98) had a modest but significant increase in concentrations of fibrinopeptide A, indicating an activated coagulation system. Concentrations of B beta 15-42 were similar in those with coronary artery disease and in the controls. The enhanced thrombin activity in coronary artery disease is in keeping with current evidence suggesting an association between coronary artery disease and a hypercoagulable state.

Adult↗

Regression of electrocardiographic left ventricular hypertrophy following treatment of primary hyperaldosteronism.

The electrocardiograms (ECGs) of a series of 34 patients with primary hyperaldosteronism (PHA), 17 treated surgically (group I) nine treated medically (group II) and eight treated with/by both surgery and drug therapy (group III) were analysed to determine whether the treatment of PHA resulted in an improvement in the ECG changes of left ventricular hypertrophy (LVH) and also whether there was a difference in this improvement between medically and surgically treated patients. There was a significant reduction of blood pressure in the group as a whole (186/111 to 141/95 mmHg, P less than 0.001) and within each of the treatment groups (group I 183/108 to 137/98 mmHg, group II 188/112 to 147/93 mmHg, group III 193/115 to 144/92 mmHg). This reduction within each group was of a similar magnitude. There were reductions in both precordial voltages (SV1 + RV5) from 3.68 mV to 2.79 mV (P less than 0.01) and in the number of patients with ECG LVH from 15 to 8 (P less than 0.05). Again the reductions were of similar magnitude in each of the groups: group I 3.78 to 2.77 mV, group II 3.78 to 2.84 mV, group III 3.39 to 2.77 mV. Thus the improvement in blood pressure achieved by the treatment of PHA is accompanied by a reduction in precordial voltages and the number of patients with ECG-LVH. This improvement is independent of the type of treatment used.

Adult↗

Severity of coronary artery disease and basal fibrinolysis.

Basal venous blood levels of several components of the fibrinolytic enzyme system (plasminogen activator, plasminogen, fibrin degradation products, alpha 2-antiplasmin, and alpha 2-macroglobulin) were measured in 100 white men with angiographically defined coronary artery disease. The tests of fibrinolysis were not related to the severity of coronary artery disease, as indicated either by the number of vessels involved or by a coronary score system. Fibrinogen levels, however, did show a modest association with the extent of coronary atheroma (r = 0.21, p less than 0.05). Triglyceride levels were associated with the inhibitors of fibrinolysis: positively with alpha 2-antiplasmin (r = 0.31, p less than 0.005) and negatively with alpha 2-macroglobulin (r = -0.25, p less than 0.05). The alpha 2-antiplasmin levels were significantly elevated in patients with hypertriglyceridaemia. Neither smoking nor beta-blockade had any effect on the tests of fibrinolysis. This study adds support to the association of plasma fibrinogen with ischaemic heart disease.

Adult↗

Effects of bezafibrate on apolipoprotein B metabolism in type III hyperlipoproteinemic subjects.

This study was designed to investigate the response of Type III hyperlipoproteinemic subjects to bezafibrate therapy. The metabolism of apolipoprotein B was examined in four lipoprotein subclasses of Sf 60-400 (large very low density lipoprotein (VLDL)), Sf 20-60 (small VLDL), Sf 12-20 (intermediate density lipoprotein (IDL)), and Sf 0-12 (low density lipoprotein (LDL)) before and during bezafibrate therapy. Treatment reduced the plasma concentration of VLDL and raised high density lipoprotein (HDL) cholesterol. There was no net change in LDL cholesterol or its associated apolipoprotein B. The decrease in plasma VLDL derived mainly from an inhibition of synthesis of both large and small subfractions which reduced the number of particles in the circulation without normalizing their lipid composition. Catabolism of the larger VLDL also increased, presumably as a result of lipoprotein lipase activation. Although the plasma concentration of LDL was unchanged, both its synthesis and catabolism were perturbed. Its fractional catabolic rate fell by 50%, but the impact that this would have had on its steady state level in the circulation was apparently blunted by a decrease in its synthesis from Sf 12-20 IDL. In the control phase of the study, most IDL apolipoprotein B was converted to LDL. Bezafibrate therapy channelled this material towards direct catabolism.

Adult↗

Effect of Ciprofibrate on platelet aggregation and fibrinolysis in patients with hypercholesterolaemia.

The fibrinolytic and platelet effects of Ciprofibrate, a new lipid lowering drug, were studied in 7 patients with hypercholesterolaemia over a 12 week period. A significant reduction in plasma fibrinogen was noted and a lesser increase in fibrinolytic activity. However, no change in platelet aggregation was noted. As expected Ciprofibrate produced a significant hypolipidaemic effect in these patients. We have described effects of Ciprofibrate which may have potential benefits in this high risk patient group.

Adult↗

A comparison of atenolol and long-acting trimazosin in mild to moderate essential hypertension.

In a 12-week double-blind randomised study the efficacy of atenolol and a new longer-acting formulation of trimazosin were compared when given once daily in patients with mild to moderate hypertension. Two parallel groups, each consisting of 18 patients, were studied. At randomisation the two groups were well matched for age and sex distribution. They were also well matched for blood pressure, pulse rate and body weight; these latter measurements were recorded at regular intervals during the 12 weeks of study. Atenolol produced substantial reduction in both systolic and diastolic blood pressure, and in heart rate, during 12 weeks of treatment. This therapeutic effect was maintained until the next dose after 24 hours. Trimazosin, by comparison, failed to reduce either systolic or diastolic pressure, or to alter heart rate. Side effects were minor with both agents and compliance with treatment was good. Atenolol caused significant elevation of plasma concentration of triglyceride, with reduction in high density lipoprotein concentration when compared with trimazosin. In conclusion, atenolol was confirmed as an effective agent for the treatment of mild to moderate hypertension. By comparison trimazosin in the longer-acting formulation was ineffective in this study. However, trimazosin may still find a place in treatment if used at higher dose.

Adolescent↗

Myocardial infarction in pregnancy.

A young women presented with an anterior myocardial infarction in the first trimester of pregnancy. Her subsequent clinical course was uneventful. Such patients appear to have a good prognosis.

Adult↗

Haematocrit in patients attending a hypertension clinic.

In view of recent interest in the relationship of haematocrit and blood viscosity to hypertension and vascular disease, we have analysed retrospectively the relationship of haematocrit to blood pressure, vascular complications and other variables in 2,381 patients referred to the Glasgow Blood Pressure Clinic. Haematocrit correlated negatively with age and systolic pressure in men, and positively with age and systolic pressure in females. Positive correlations were found in both sexes between haematocrit and serum alanine aminotransferase (possibly due to mutual correlation with alcohol); and between haematocrit and overweight (Quetelet Index) but not obesity (Ponderal Index). Increased haematocrit was also associated with cigarette smoking; and with history of angina, myocardial infarction and intermittent claudication in females. No correlation was observed between haematocrit and history of stroke. These findings suggest that prospective studies of haematocrit in hypertensives may be of interest.

Adult↗