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Biomedical subjects

A R Lorimer

Publications and source records attributed to A R Lorimer.

At least 73 records · Page 4Linked to original sources
PubMed1985

Serum oestradiol and ischaemic heart disease--relationship with myocardial infarction but not coronary atheroma or haemostasis.

Elevated oestradiol (E2) levels may be a risk factor for ischaemic heart disease in men, although the mechanisms for the elevation of oestrogen and for its adverse effects remain unclear. We have studied 100 Caucasian males undergoing elective coronary angiography for ischaemic chest pain and measured serum oestradiol, a profile of haemostatic tests, extent of coronary artery disease and evidence of previous myocardial infarction in order to assess any relationships which could explain the effect of elevated serum oestradiol levels. Levels were significantly higher in men with a history of myocardial infarction compared to those without (p less than 0.01), but were unrelated to the extent of coronary disease or to the haemostatic tests. These results suggest that the association of oestradiol with coronary events relates to myocardial infarction, not to atherogenesis, and is not due to any currently measurable alterations of haemostasis. Current beta-adrenoceptor blocker treatment was associated with lower oestradiol and thromboxane B2 concentrations (both, p = 0.06). These incidental findings suggest that further studies of the effects of beta-blockade on oestradiol and thromboxane metabolism are indicated.

Adrenergic beta-Antagonists↗
PubMed1984

Response of femoral venous oxygen tension to graduated pressure stockings--possible relationship to deep vein thrombosis.

Venous oxygen tension (pO2) was measured in discrete samples of blood obtained through the femoral vein of cardiac catheterisation patients before, during and after application of sustained external graduated pressure in the form of compression stockings (T. E. D. Kendall). There was a significant reduction (p less than 0.05) of pO2 from the baseline value both 30 sec and one minute after the application of the pressure stockings. Thereafter, the pO2 rose to baseline values. Two minutes after the stockings were removed there was again a significant reduction (p less than 0.05) of pO2 from the baseline value. We suggest that the decrease in venous pO2 on application of external pressure may be a reflection of washing out of stagnant hypoxic blood from the venous valve pockets, which may be related to the formation of deep vein thrombosis (DVT).

Blood Gas Analysis↗
PubMed1984

"Third drug" trial: comparative study of antihypertensive agents added to treatment when blood pressure remains uncontrolled by a beta blocker plus thiazide diuretic.

Hydralazine, labetalol, methyldopa, minoxidil, prazosin, and placebo were compared when added by random allocation to atenolol 100 mg and bendrofluazide 5 mg daily in a series of 238 hypertensive patients inadequately controlled by the beta blocker-diuretic combination. Atenolol was withdrawn in those allocated to labetalol, and minoxidil was given only to men. The order of acceptability was: placebo, hydralazine, prazosin, methyldopa, minoxidil, labetalol. Minoxidil was more effective than the other active drugs, which had similar potency to one another. All the active agents were more effective than placebo. Hydralazine was the most generally suitable third drug, with prazosin a close second. Minoxidil was especially effective in patients with less severe hypertension but the same regimen caused fluid retention in those with more severe disease. Labetalol should probably be introduced at a low dose (150 mg daily) even when replacing full doses of a previously administered beta blocker.

Adolescent↗
PubMed1984

Calcium antagonists and endocrine status: lack of effect of oral verapamil on pituitary-testicular and pituitary-thyroid function.

Calcium ions seem to be essential for the release of many hormones. The calcium antagonist verapamil which is used as an anti-arrhythmic and anti-anginal agent has an inhibitory effect on the release of follicle stimulating hormone (FSH), luteinising hormone (LH), and thyrotrophin stimulating hormone (TSH) when given as an intravenous infusion to normal volunteers. As verapamil is usually given orally we studied pituitary-testicular and pituitary-thyroid function before and after completing a 4-week course of oral verapamil. The oral preparation did not have any significant effect on the endocrine parameters studied.

Administration, Oral↗
PubMed1984

Comparison of three adrenoreceptor blocking agents in patients with cirrhosis and portal hypertension.

The effects of different types of adrenoreceptor blocking agents on portal venous pressure were studied in patients with cirrhosis and portal hypertension. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta 1 and beta 2 blocker), and prazosin (alpha blocker) were compared in three groups of eight patients. Haemodynamic measurements were made before and after two or three and eight weeks of therapy. The dose of beta blockers was sufficient to reduce the exercise heart rate by more than 25%. Propranolol and prazosin produced a sustained reduction in the mean portohepatic venous pressure gradient of the order of 25% and 18% respectively. The cardiac index was significantly reduced by propranolol but not altered by prazosin. Atenolol produced an early reduction in portohepatic venous pressure which, although not sustained, showed a good correlation with reduction in cardiac index. No such relationship was found with propranolol. All three drugs were well tolerated by these patients with advanced cirrhosis. Therefore propranolol and prazosin have proved to be effective agents for the reduction of portal venous pressure.

Atenolol↗
PubMed1984

Apolipoprotein A and B (Sf 100-400) metabolism during bezafibrate therapy in hypertriglyceridemic subjects.

This study describes the effects of bezafibrate, an analogue of clofibrate, on the plasma lipid and lipoprotein profiles of 11 hypertriglyceridemic subjects and on their metabolism of apolipoproteins A-I, A-II, and B. The major action of the drug was to lower plasma triglyceride (by 58%; P less than 0.01). This was accompanied by a reduction in the level of very low density lipoprotein apoprotein B (Svedberg units of flotation [Sf] 60-400), whose mean residence time in the plasma fell threefold (from 3.4 to 1.0 h). Synthesis of the B protein in this fraction was not significantly altered, so the drug acts to accelerate the transit of very low density lipoprotein particles down the delipidation cascade. The metabolism of very low density lipoprotein remnant apoprotein B (Sf 12-100) changed little in response to treatment, although we detected a 30% increment (P less than 0.05) in the plasma concentration of this fraction. The mean residence time of these remnant particles in the plasma did not correlate with that of Sf 100-400 very low density lipoprotein apoprotein B, nor was this parameter altered by the drug. The most consistent and significant perturbation seen in the Sf 0-12 fraction (low density lipoprotein) was a reduction in the fractional catabolism of its apoprotein B moiety (26%; P less than 0.05). In those subjects who were grossly hypertriglyceridemic and who responded well to treatment, the level of this protein rose substantially owing to a combined increase in its synthesis and a reduction in its catabolism. In the group as a whole, high density lipoprotein cholesterol rose 13% (P less than 0.02), and detailed examination showed that this was associated with a small but significant increment in the plasma concentration of the high density lipoprotein subfraction 2. High density lipoprotein subfraction 3 also rose on the average, but this was not a consistent feature in all patients. The plasma concentrations and turnovers of the A proteins (A-I and A-II) were not significantly altered by bezafibrate therapy.

Apolipoproteins A↗
PubMed1984

Metabolism of apolipoprotein B in large triglyceride-rich very low density lipoproteins of normal and hypertriglyceridemic subjects.

The metabolic fate of very low density lipoprotein can be examined by following the transit of its apolipoprotein B moiety through the delipidation cascade, which leads to low density lipoprotein. In this study we have used cumulative flotation ultracentrifugation to follow the metabolism of various lipoprotein subclasses that participate in this process in normal, hypertriglyceridemic (Type IV), and dysbetalipoproteinemic (Type III) subjects. Large triglyceride-rich very low density lipoproteins of Svedberg units of flotation (Sf) 100-400 were converted virtually quantitatively in normal subjects to smaller Sf 12-100 remnant particles. Only a minor fraction appeared thereafter in low density lipoproteins (Sf 0-12), most being removed directly from the plasma. Type IV hyperlipoproteinemic individuals converted the larger Sf 100-400 very low density lipoproteins to intermediate particles at approximately 50% of the control rate but thereafter their metabolism was normal (fractional clearance of Sf 12-100 particles in controls, 1.29 +/- 0.23 pools/d; in Type IV hypertriglyceridemics, 1.38 +/- 0.23 pools/d; n = 4 in each case). Since the apolipoprotein B in large triglyceride-rich particles did not contribute significantly to the mass of the low density lipoprotein apoprotein pool, the latter must come largely from another source. This was examined by following the metabolic fate of small very low density lipoproteins of Sf 20-60 or of the total lipoprotein spectrum of d less than 1.006 kg/liter (approximate Sf 20-400). The small particles were rapidly and substantially converted to low density lipoproteins, suggesting that the major precursor of the latter was to be found in this density range. Whereas only 10% of apolipoprotein B in Sf 100-400 lipoproteins reached the low density lipoprotein flotation range, greater than 40% of Sf 20-100 B protein eventually appeared in Sf 0-12 particles; and when very low density lipoprotein of d less than 1.006 kg/liter is used as a tracer of apolipoprotein B metabolism it is primarily this population of small very low density lipoprotein particles in the Sf 12-100 flotation range that is labeled. A detailed examination was made of apolipoprotein B metabolism in three dysbetalipoproteinemic subjects. The plasma clearance curves of their Sf 100-400 lipoproteins were distinctly biphasic. The quickly decaying component converted rapidly into remnants of Sf 20-60 at a near normal rate (0.56 vs. 0.62 pools/d in normal subjects). Its subsequent processing, however, was retarded. The more slowly catabolized fraction, comprising 30% of the total apolipoprotein B radioactivity, had no counterpart in normal or Type IV hyperlipoproteinemic individuals. These data, taken together, suggest that the very low density lipoprotein consists of a complex mixture of particles with different origins and fates. Within the Sf 20-100 flotation range there are at least two subcomponents. One represents remnants of larger triglyceride-rich particles which are catabolized slowly and feeds little apolipoprotein B into low density lipoprotein. The other is apparently secreted directly into this flotation interval and transfers significant amounts of B protein rapidly into Sf 0-12 lipoproteins.

Apolipoproteins B↗
PubMed1983

Oral verapamil does not affect glucose tolerance in non-diabetics.

Verapamil, a calcium antagonist used to treat angina pectoris, inhibits insulin release in vitro and, when administered intravenously to humans, decreases glucose tolerance. Oral verapamil, 120 mg/day for 1 week increasing thereafter to 240 mg/day in divided doses, was given to nine non-diabetic patients with angina pectoris for 4 weeks. The glucose and insulin responses to a standard glucose load showed no significant difference before and after verapamil. Oral verapamil in the doses used in this study had no significant effect on glucose tolerance in non-diabetics.

Adult↗
PubMed1983

The 'third drug' trial: a comparative study of anti-hypertensive agents added to treatment when blood pressure is uncontrolled by a beta-blocker plus thiazide diuretic.

Hydralazine, labetalol, methyldopa, minoxidil, prazosin and placebo were compared when added to atenolol 100 mg and bendrofluazide 5 mg daily in hypertensive patients inadequately controlled by the beta-blocker/diuretic combination. Atenolol was withdrawn in those allocated to labetalol and minoxidil was given only to men. The order of acceptability was: placebo, hydralazine, prazosin, methyldopa, minoxidil, labetalol. All the active agents were more effective than placebo. Minoxidil was more effective than the other active drugs, which had similar potency to one another. Hydralazine was the most generally suitable third drug, with prazosin a close second. Minoxidil was effective in the milder hypertensives, but in the present regimen caused fluid retention in those with more severe hypertension. Labetalol probably should be introduced at lower dose (150 mg daily) even as replacement for full doses of a previously administered beta-blocker.

Adolescent↗
PubMed1983

An evaluation of the effect on resting and exercise blood pressure of some first line treatments in hypertension.

Eighteen patients with idiopathic hypertension were studied to assess the anti-hypertensive control, both at rest and during exercise of increasing doses of hydrochlorothiazide, metoprolol and a combination of hydrochlorothiazide and metoprolol. Each active treatment period was given for four weeks with an intervening four week placebo period, with assessments made at 2 to 4 hours and 22 to 24 hours following tablet intake. The results show that the resting systolic and diastolic values for all active treatment periods were significantly different from placebo. During exercise, the systolic blood pressure levels were significantly reduced by all active treatments with the greatest overall reduction being achieved by either metoprolol or the metoprolol-hydrochlorothiazide combination. However, the exercise induced increase in systolic blood pressure was reduced by approximately 25% by both metoprolol and the combination product, when compared to placebo, but not by the diuretic alone.

Adult↗
PubMed1983

The hypolipidemic action of probucol: a study of its effects on high and low density lipoproteins.

This study examines the effects of probucol (1 g/day) on the plasma concentration, composition, and metabolism of low and high density lipoproteins (LDL and HDL) in eleven hyperlipidemic subjects, (seven Type II and four Type IV). The drug lowered plasma cholesterol in the Type II patients by 11% (P < 0.02) without affecting triglyceride. Both LDL and HDL cholesterol levels fell by 6% and 26%, respectively. The small reduction in the former was not associated with a change in the composition of the lipoprotein nor with a measurable alteration in the level of circulating apoLDL. Kinetic studies revealed that probucol had no consistent effect on either the synthesis or catabolism of apoLDL. However, probucol did exert a potent influence on HDL, lowering the level of this lipoprotein in both the Type II and Type IV patients despite the fact that total plasma cholesterol in the latter group was unchanged by treatment. The fall in HDL mass largely affected the HDL(3) subfraction; HDL(2), which was initially low in our subjects, did not show a consistent response to therapy. Not all of the constituents in HDL were equally affected by the drug. Specifically, the fall in total plasma apoA levels (which derived from significant reductions in the rates of synthesis of apoproteins A-I and A-II) was less than that of HDL cholesterol. Direct measurement of the composition of the lipoprotein confirmed that during therapy it carried less cholesterol per unit protein. The significance of these observations in relation to the prophylaxis of ischemic heart disease is not yet clear, but it seems prudent at present to use probucol selectively in subjects who show a substantial hypocholesterolemic response that derives primarily from a reduction in circulating LDL.-Atmeh, R. F., J. M. Stewart, D. E. Boag, C. J. Packard, A. R. Lorimer, and J. Shepherd. The hypolipidemic action of probucol: a study of its effects on high and low density lipoproteins.

Adult↗
PubMed1982

Increased blood viscosity and fibrinolytic inhibitor in type II hyperlipoproteinaemia.

Blood rheology and several haemostatic factors were studied in patients with type II hyperlipoproteinaemia (HLP) and matched controls. HLP patients had increased blood viscosity (p less than 0.01), the mean level being 18% higher at a low shear-rate (0.94 s-1) and 13% higher at a high shear-rate (94 s-1). The increased viscosity was due partly to a raised haematocrit (p less than 0.05), and partly to increased plasma viscosity (p less than 0.01) associated with increased plasma fibrinogen (p less than 0.02). Red cell deformability was normal, and viscosity was unrelated to either lipid or lipoprotein concentrations. Levels of the major fibrinolytic inhibitor. alpha 2-antiplasmin, measured by both functional and immunological techniques were higher in HLP patients (mean increase 30-32%). Plasminogen activator levels were normal in HLP patients and the ratio of fibrinolytic inhibitor to activator was therefore increased. Plasminogen concentrations were also increased. Levels of factor VIII activity and antigen, antithrombin III and anti-factor Xa activity, alpha 2-macroglobulin, platelet count, and platelet aggregation by adenosine diphosphate and adrenaline did not differ significantly in HLP patients and controls. These results suggest that the premature arterial disease associated with HLP may be related to increased blood viscosity, which reduces arterial blood flow, and increased alpha 2-antiplasmin, the major inhibitor of fibrinolysis.

Adolescent↗
PubMed1982

Effects of bezafibrate on receptor-mediated and receptor-independent low density lipoprotein catabolism in type II hyperlipoproteinaemic subjects.

This study examines the effects of bezafibrate (200 mg t.i.d.) on LDL metabolism in 7 type II hyperlipoproteinaemic subjects. Eight weeks of treatment lowered plasma cholesterol and triglyceride by 10% and 30%, respectively (P less than 0.02). These reductions were associated with a fall in circulating VLDL (31%, P less than 0.02) and LDL (11%, P less than 0.05), while HDL cholesterol stayed the same. LDL metabolism changed during therapy. The plasma fractional clearance rate (FCR) of autologous [125I]LDL normalized from a low value of 0.256 +/- 0.048 (mean +/- SD) to 0.298 +/- 0.040 pools/day (P less than 0.001). This was attributable to a 65% increase (P less than 0.01) in receptor-mediated LDL catabolism since the clearance of simultaneously injected 1,2-cyclohexanedione-modified [131I]LDL, which measures the receptor-independent pathway, was unaltered (FCR of [131I]cyclohexanedione/LDL in control phase = 0.194 +/- 0.030 pools/day; during drug treatment = 0.194 +/- 0.024 pools/day). We conclude that bezafibrate lowers plasma LDL in type II hyperlipoproteinaemia by promoting its degradation via high affinity receptors.

Adult↗
PubMed1981

Bayesian analysis of stress thallium-201 scintigraphy.

The variation of the diagnostic value of stress Tl-201 scintigraphy with prevalence of coronary heart disease (CHD) in the population has been investigated using Bayesian reasoning. From scintigraphic and arteriographic data obtained in 100 consecutive patients presenting with chest pain, the sensitivity of stress Tl-201 scintigraphy for the detection of significant CHD was 90% and the specificity was 88%. From Bayes' Theorem, the posterior probability of having CHD for a given test result was calculated for prevalences of CHD ranging from 1% to 99%. The discriminant value of stress Tl-201 scintigraphy was best when the prevalence of CHD lay between 30% and 70% and maximum for a prevalence of 52%. Thus, stress Tl-201 scintigraphy would be an unsuitable diagnostic test where the prior probability of CHD is low, e.g., population screening programmes, and would add little where the clinical probability of having CHD is already high. However, where the prior probability of having CHD is intermediate stress Tl-201 scintigraphy may provide valuable diagnostic information.

Bayes Theorem↗